Effect of cyclosporin on plasma lipoprotein lipase activity in rats.

The effects of cyclosporin on plasma lipoproteins and lipoprotein lipase (LPL) activity were studied in rats treated with different doses of the drug for periods ranging between 7 and 30 days. The treatment with cyclosporin resulted in an increase in plasma triglycerides and non-HDL-cholesterol, and a dose and time-dependent decrease of LPL activity and HDL-cholesterol, mainly because of a fall in the HDL2-cholesterol subfraction. The decrease of LPL activity was positively correlated (p < 0.01) with plasma HDL-cholesterol and HDL2-cholesterol and negatively with plasma triglycerides and non-HDL-cholesterol (p < 0.01). Our results indicate that the decrease in plasma LPL activity may be responsible for the increase in plasma triglycerides and the decrease in plasma HDL-cholesterol found in rats under cyclosporin treatment.


Probucol, incorporated into LDL particles in vivo, inhibits generation of lipid peroxides more effectively than endogenous antioxidants alone.

One of the first steps in lipid autoxidation leads to the generation of lipid peroxides (LPO). The time course of LPO generation during Cu++ catalyzed oxidation of LDL before and after treatment with probucol was determined in this study. Before analysis the samples had been stored for about 3 years at -20 degrees C. The results show that in LDL samples without probucol the total antioxidative potential had been depleted during the long-term storage. In contrast, LDL containing probucol showed almost no signs of lipid autoxidation. In addition, the ratio of vitamin E to cholesterol was significantly higher in serum samples containing probucol. We conclude that, in vivo, probucol is incorporated into LDL particles in concentrations high enough to inhibit even early steps of lipid autoxidation.


[Magnetic resonance imaging in multiple system atrophy].

We studied 18 patients with multiple system atrophy (MSA) by high field strength MRI: 6 striatonigral degeneration (SND), 4 Shy-Drager syndrome (SDS), and 8 olivo-ponto-cerebellar atrophy (OPCA). We also studied 30 Parkinson's disease (PD) and 10 age-matched controls. The diagnoses of SND, SDS, and OPCA were based on criteria after Hirayama et al (1985). Bradykinesia, rigidity, and tremor were assessed with the summed scores of the signs used as the extrapyramidal scores. The mean extrapyramidal scores were not significantly different in patients with SND, SDS, OPCA, and PD. MRI studies were performed on 1.5 tesla MRI unit, using a T2 weighted spin echo pulse sequence (TR2500 ms/TE40 ms). The width of the pars compacta signal in all subjects was measured by the method of Duguid et al (1986). Intensity profiles were made on a straight line perpendicular to the pars compacta through the center of the red nucleus on an image of the midbrain. We measured the width of the valley at half-height between the peaks of intensity representing the red nucleus and the crus cerebri-pars reticulata complex and used this measurement as an index of the width of the pars compacta signal. The mean widths of the pars compacta signal were: 2.8 +/- 0.4 mm (SND), 2.8 +/- 0.7 mm (SDS), 3.6 +/- 0.6 mm (OPCA), 2.7 +/- 0.3 mm (PD), and 4.3 +/- 0.6 mm (control). The mean widths of the pars compacta signal in PD, SND, and SDS were significantly narrower than that in the control group (p < 0.05), while the OPCA group was not significantly narrower.(ABSTRACT TRUNCATED AT 250 WORDS)


[On stuttering-like hesitation resulting from infarct in the midbrain and the mesial thalami].

We described a patient who developed stuttering after an infarct both in the midbrain and the medial part of bilateral thalami. Previously, speech disturbance resulting from these lesions has been named palilalia. However, we differentiated such a speech disturbance from both stuttering and palialia, because it had high frequency of repetition and monotonous rhythm, and because repetition was observed more frequently in the head of words than in the middle or the end of words. We proposed to call this speech abnormality stuttering-like hesitation in order to differentiate it from ordinary stuttering or palilalia. As the causative lesion for stuttering-like hesitation, we proposed the lesion in the neuronal circuit including the supplementary motor area and its afferent pathways, in addition to the lesion in the extrapyramidal system.


[Cerebral blood flow distribution and reactivity during the symptom-free stages of transient ischemic attacks--a 99mTc-HMPAO SPECT study].

Even during the symptom-free stages, patients with transient ischemic attacks (TIA) often show cerebral blood flow (CBF) disturbances. For evaluating the factors which cause these abnormalities, we studied CBF and CBF reactivity to acetazolamide (Diamox) using a 99mTc-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT). The results from CBF-SPECT were compared with X-ray computed tomography (CT), cerebral arteriogram, clinical characteristics of TIA and cerebrovascular risk factors. The overall sensitivity rates in detecting the lesion were 68% in CBF-SPECT and 9% in CT. The size of the hypoperfused area tended to be wide in patients who had intracranial, severe stenotic or multiple arterial lesions on the ipsilateral side. No such relations were found between CBF and other examinations. Brain hypoperfusion was located in the subcortical region in eight patients; two patients showed a small hypodense lesion on CT which corresponded to the hypoperfusion on SPECT, and three patients showed no arteriographic abnormality. Hypoperfusion in the cortex was seen in seven patients; all patients showed arteriographic abnormality, but no CT abnormality. The severity rating of the vascular stenosis and hypoperfusion, and the incidence of the intracranial lesions were higher in this group than the group with subcotical hypoperfusion. Seven patients showed fixed normoperfusion before and after diamox injection. Two patients with a subcortical small infarction showed fixed hypoperfusion even after diamox injection. Twelve patients showed focal hypoperfusion before diamox with a new filling-in after diamox. Only one patient showed resting hypoperfusion and decreased CBF reactivity to diamox.(ABSTRACT TRUNCATED AT 250 WORDS)


[A case of progressive hemiatrophy with type 2 muscle atrophy in muscle biopsy].

We reported a case of progressive hemiatrophy, whose skeletal muscle biopsy revealed type 2 fiber atrophy. This patient, a 40-year-old woman, noticed left leg atrophy at the age of 39. She had a history of minor trauma of the left thigh at the age of 30. On admission, physical examination revealed atrophy of various parts of her left side of body, predominantly in the left leg. There was no dermatological or neurological abnormalities except these atrophies. Hematological and biochemical examinations were normal. EEG, EMG, nerve conduction studies and autonomic function tests were normal in either side of the body. MRI study showed reduced muscle bulk as well as subcutaneous fatty tissue especially in her left leg. Skeletal muscle biopsy of her left quadriceps femoris muscle revealed type 2 fiber atrophy and type 1 fiber predominance. However, no abnormality was found in the intramuscular nerves. We considered that type 2 muscle fiber atrophy was one of the cause of atrophy of this case.


[MRI findings of brain-stem tuberculoma in a case of tuberculous meningitis].

A 54-year-old woman developed headache and slight fever. When she consulted a physician, she could not move either of her eyes to the right. Cranial CT scan revealed no significant findings. Lumbar puncture was performed and CSF examination showed the cell count of 10,304/mm3, glucose level of 10 mg/dl, and total protein value of 270 mg/dl. Her symptoms and laboratory findings suggested meningitis and she was admitted to our hospital. Neurological examination revealed bilateral dilated pupils with sluggish light reflex, right gaze palsy, and hypesthesia of the left side of her face. A diagnosis of tuberculous meningitis was established by a positive test for acid-fast bacillus in CSF, and anti-tuberculous therapy was started at once. One month after the onset of symptoms, her main complaints were double vision and cerebellar ataxia. Both CT and MRI revealed a right brain-stem lesion. Pre-contrast CT could not clearly visualize the lesion but with contrast medium a homogeneously-enhanced circular lesion was shown. MRI on T2WI demonstrated the right brain-stem lesion to have a central bright core with hypointense periphery, which in turn was surrounded by hyperintensity. The lesion appeared isointense with cerebral white matter and the "central bright core" area was demonstrated to be slightly hypointense on T1WI. On post-contrast T1WI (with Gd-DTPA), the lesion showed strong homogeneous enhancement. The CT and MRI findings indicated a brain-stem tuberculoma, which was regarded as the cause of the ocular movement paralysis and cerebellar ataxia. As the clinical symptoms gradually resolved with anti-tuberculous treatment, the MRI appearance of the lesion also improved.(ABSTRACT TRUNCATED AT 250 WORDS)


[Palilalia and acquired stuttering in a case of Parkinson's disease].

We report palilalia and acquired stuttering in a 60-year-old Japanese male with Parkinson's disease. At the age of 54, he presented with resting tremor in the hand and foot on the left, and gradual slowness in voluntary movements. Two years later, resting tremor involved the right foot, and an expressionless face and frozen gait occurred. A diagnosis of Parkinson's disease was made and treatment with L-dopa and carbidopa resulted in conspicuous improvement. At the age of 57, he developed compulsive repetitions of syllables, words and phrases, and sentences infrequently when he spoke. They have been persisting for four years. Repetitions increased in spontaneous speech while they decreased in oral reading and repetition of sentences. These repetitions in speech were symptomatologically diagnosed as palilalia and acquired stuttering. Brain CT showed slight brain atrophy, and brain MRI disclosed a few lesions indicating lacunae in the left substantia nigra, left putamen, and right internal capsule. SPECT showed a slight decrease in blood flow in the frontal lobes and basal ganglia bilaterally. Full IQ on WAIS was 105, and neither agnosia nor apraxia was detected. Palilalia and acquired stuttering, though the pathomechanism has not been clarified, have been reported to occur usually secondary to cerebral vascucular lesions and very rarely in Parkinson's disease. In the present case, they may have been produced by the parkinsonian nigro-striatal lesions. Alternatively, they may have been induced by the small vascular lesions demonstrated by MRI.


[Myoclonus epilepsy associated with ragged-red fibers--report of a patient with negative myoclonus].

A 21-year-old woman, who had no particular familial history, was admitted to our hospital because of hand tremor and gait disturbance. On neurological examination, she showed muscle weakness in the proximal extremities. There was an ataxia on heel-to-shin testing. Action and postural myoclonus involving the extremities were also noted. In addition, with dorsiflexion of the hands, asterixis-like movement was manifested. Pyruvate was 1.0 mg/dl and lactate was 24.1 mg/dl in cerebrospinal fluid. Brain CT scan revealed mild cerebellar atrophy. EEG showed synchronous diffuse slow wave. Median nerve SEPs showed a large N20-P25 component (20 microV). Median nerve C-reflex was not evoked. With dorsiflexion of the hands, the asterixis-like movement was induced with brief cessation of surface EMG activity in the forearm muscles, as shown by the accelerometer trace. Biopsy specimens of the biceps brachii muscle revealed numerous ragged-red fibers. By PCR-RFLP method with use of a mismatched primer, we analyzed mitochondrial DNA extracted from peripheral leukocytes. The A to G mutation at nucleotide position 8,344 in a tRNA(Lys) gene of a mitochondrial genome was detected. In this patient, clonazepam was effective on the asterixis-like movements. From existence of positive myoclonus, giant SEPs and efficacy of clonazepam, we considered this movement to be negative myoclonus. Our study indicated the possibility that such an involuntary movement could be induced by certain posture in patients with MERRF.


[A case of benign intracranial hypertension with fluctuated symptoms and CSF pressure synchronized with menstrual cycle].

A 39-year-old woman presented with a 2-month history of repeated severe headache, nausea and diplopia. On admission she was obese with bilateral papilledma and abducens weakness. Mass lesion and sinus thrombosis were ruled out by brain CT and angiography. CSF pressure was normal initially. CSF pressure fluctuated with menstrual cycle, sometimes showing over 600 mmH2O with worsening of the symptoms. She was diagnosed as benign intracranial hypertension (BIH). Diuretics did not improve the symptoms, and visual disturbances ensued and deteriorated. A spinal subarachnoid space-peritoneal shunt was inserted to control CSF pressure, showing rapid improvement of headache and diplopia but visual disturbances remained almost unchanged. Optic nerve sheath fenestration was performed without improvement of visual deterioration. We postulated multiple factors such as obesity, menstrual abnormality, iron deficiency anemia and analgesic drugs played important roles to produce BIH in this case. Careful quantitative perimetry should be done to decide a suitable time for surgical treatment in BIH.


[A case of myasthenia gravis occurring in the period of remission of chronic inflammatory demyelinating polyradiculoneuropathy].

A 31-year-old woman noticed progressive muscular weakness in the limbs and paresthesia in the fingers in February 1989. Paresthesia worsened and improved 4 times during 2 months. Intravenous edrophonium chloride failed to improve her muscular weakness. She had high antiacetylcholine receptor antibody titer in serum. We made a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) because of slow nerve conduction velocity (NCV), increased CSF protein, and the clinical course. Treatment with prednisolone improved muscular weakness and the slow NCV. Two years later she acutely had dyspnea, dysphagia, and muscular weakness after upper respiratory infection. Intravenous edrophonium chloride dramatically improved her symptoms. The diagnosis was made as myasthenia gravis (MG). After thymectomy her weakness was getting better without any medications. There may exist an autoimmune mechanism common, at least in part, to both CIDP and MG in our patient.


[Gerstmann-Sträussler-Scheinker disease with heterozygous codon change at prion protein codon 129].

A 53-year-old male was admitted to our hospital for progressive dementia and gait disturbance which had started at the age of 48. Examination indicated dementia, dysarthria, dysphagia, bilateral pyramidal signs, apraxia of the limbs, and extrapyramidal signs such as fine finger tremors, and rigidity of limbs. There were no cerebellar signs or myoclonus. His mother and elder brother showed similar symptoms and died at the ages of 53 and 50, respectively. EEG was normal. CT and MRI showed mild brain atrophy, but no cerebellar atrophy. T2 weighted image indicated low intensity areas covering bilateral caudate nuclei and putamina. A heterozygous amino acid change from methionine to valine was noted at codon 129 of the prion protein of the patient as well as in one of his son. The most likely diagnosis was Gerstmann-Sträussler-Scheinker (GSS) disease without cerebellar atrophy. GSS may include a broad spectrum of brain pathology. Whether the codon change is associated with pathology without cerebellar atrophy is a problem that awaits further investigation.


[Unilateral abolition of parkinsonian rigidity after subthalamic nucleus hemorrhage].

A 63-year-old man with parkinsonism suddenly developed a right hemiballism, and the CT showed a hematoma of the left subthalamic nucleus. After the ballistic movement had disappeared, muscular rigidity improved on the right. This case suggests that excessive output from the subthalamic nucleus to the internal segment of globus pallidus plays a critical role in the pathophysiology of parkinsonian rigidity.


[The neuroendocrinological examinations in mentally retarded boy with self-injurious behavior (SIB) and the effect of naloxone, clomipramine and sulpiride on SIB].

The neuroendocrinological examinations were performed in mentally retarded 7-year-old boy with severe self-injurious behavior (SIB). The thyroid-stimulating hormone (TSH) and prolactine responses to TRH showed lower in the basal and peak levels compared with those in the age matched control group. It is suggested that there may be an enhanced dopaminergic activity. The effects of naloxone, clomipramine and sulpiride on the frequency of SIB were investigated in this case. The frequency of SIB was reduced by sulpiride; a dopamine antagonist. These data suggest dopaminergic supersensitivity and hypothalamic dysregulation as a mechanism underlying SIB.


From Monroe to Moreau: an analysis of face naming errors.

Functional models of face recognition and speech production have developed separately. However, naming a familiar face is, of course, an act of speech production. In this paper we propose a revision of Bruce and Young's (1986) model of face processing, which incorporates two features of Levelt's (1989) model of speech production. In particular, the proposed model includes two stages of lexical access for names and monitoring of face naming based on a "perceptual loop". Two predictions were derived from the perceptual loop hypothesis of speech monitoring: (1) naming errors in which a (correct) rare surname is erroneously replaced by a common surname should occur more frequently than the reverse substitution (the error asymmetry effect); (2) naming errors in which a common surname is articulated are more likely to be repaired than errors which result in articulation of a rare surname (the error-repairing effect). Both predictions were supported by an analysis of face naming errors in a laboratory face naming task. In a further experiment we considered the possibility that the effects of surname frequency observed in face naming errors could be explained by the frequency sensitivity of lexical access in speech production. However, no effect of the frequency of the surname of the faces used in the previous experiment was found on face naming latencies. Therefore, it is concluded that the perceptual loop hypothesis provides the more parsimonious account of the entire pattern of the results.


Regular and irregular inflection in the acquisition of German noun plurals.

In this paper we study the acquisition of German noun plurals in relation to the question of how children represent regular and irregular inflection. Pinker and Prince (1992) have demonstrated several dissociations between regular and irregular inflection in the English past tense system. However, in English, the default status of -ed is confounded with its high frequency; therefore inflectional systems other than English past tense formation must be examined. The noun plural system in German is particularly interesting, because most nouns have irregular plurals in German and the regular (default) plural is less frequent than several of the irregular plurals. Thus it is unclear how a language learner determines whether German even has a regular plural, and if so what form it takes. Based on longitudinal data from impaired and unimpaired monolingual German-speaking children, we find a striking, statistically significant correlation: plural affixes that are used in overregularizations, namely -n or -s, are left out within compounds. This correlation shows that even impaired children are sensitive to the distinction between regular and irregular morphology. We propose a linguistic analysis of the correlation in terms of Kiparsky's (1982, 1985) level-ordering model plus an additional ordering condition on affixes: default (regular) affixes cannot serve as input to compounding processes.


The source of belief bias effects in syllogistic reasoning.

In studies of the belief bias effect in syllogistic reasoning, an interaction between logical validity and the believability of the conclusion has been found; in essence, logic has a larger effect on unbelievable than on believable conclusions. Two main explanations have been proposed for this finding. The selective scrutiny account claims that people focus on the conclusion and only engage in logical processing if this is found to be unbelievable; while the misinterpreted necessity account claims that subjects misunderstand what is meant by logical necessity and respond on the basis of believability when indeterminate syllogisms are presented. Experiments 1 and 2 compared the predictions of these two theories by examining whether the interaction would disappear if only determinate syllogisms were used. It did, thus providing strong support for the misinterpreted necessity explanation. However, the results are also consistent with a version of the mental models theory, and so Experiment 3 was carried out to compare these two explanations. The mental models theory received strong support, as it did also in the follow-up Experiments 4 and 5. It is concluded that people try to construct a mental model of the premises but, if there is a believable conclusion consistent with the first model they produce, then they fail to construct alternative models.


Factors associated with outcome in blunt aortic injury: a population-based study.

A population-based study was conducted for two contiguous states representing a population of 9.1 million to determine whether age, injury severity score, major complications, and preexisting conditions contribute to the outcome of patients diagnosed with blunt traumatic aortic injury. A secondary analysis reviewed patients with blunt aortic injury admitted over a six-year period to a trauma center located in one of the states to examine other more detailed factors related to mortality. Age was the only variable that correlated statistically with mortality in both populations analyzed. (Region P = .004; trauma center P = .0012) The severity of injury showed a tendency for decreased survival with increasing injury severity score. The elderly (age > or = 55) in both data sets sustained higher mortality from blunt aortic injury. In the trauma center population, the elderly had more delay in diagnosis than the younger patient population.


Surgical potpourri.

Six unusual surgical case are reported and the literature reviewed. The cases are: 1. Adenoid cystic carcinoma of the submaxillary gland 2. Parathyroid carcinoma 3. Squamous cell cancer of the pancreas 4. Leiomyosarcoma of the abdomen (two cases) 5. Myelolipoma of the adrenal gland These are representative cases from a general surgeon's practice, emphasizing the variety of interesting patients that the general surgeon cares for, and the scope of surgical knowledge that must be continually maintained. One of the attractions of having a practice in general surgery is that it provides the opportunity to diagnose and treat patients with a variety of conditions requiring surgical intervention. Reviewed here are six recent operative cases, their presentation, and management.


Topographical differences in cell area at the surface of the corneal epithelium of the pigmented rabbit.

Corneas from female pigmented rabbits were prepared for scanning electron microscopy at 15.00 h. The superior-temporal and inferior-nasal quadrants were evaluated at 500X at-stage magnification, normal to the corneal surface, at central, paracentral and peripheral sites. Non-parametric statistical analyses of the histograms of cell surface areas at each site from seven corneas revealed significant differences between the three sites but not between superior and inferior quadrants.


Functional characterization of insulin and IGF-I receptors in chicken lens epithelial and fiber cells.

Insulin and insulin-like growth factor I (IGF-I) play a role in lens cell growth and development. The binding of these hormones to their respective receptors with its concomitant signal transduction is an important step in these cellular processes. Hormone binding to adult chicken lens insulin and IGF-I receptors, partially purified from epithelial and fiber cells, was studied to examine this activity in lens. The associated stimulation of receptor-mediated tyrosine kinase by the hormones was also studied. At an insulin concentration of 0.02 nM, specific binding was similar for epithelial and fiber receptor preparations (Epi = 0.23 +/- 0.03 fmol, Fib = 0.19 +/- 0.02 fmol). Displacement studies revealed that there was also no difference between epithelial and fiber receptor preparations in the concentration of insulin necessary for half maximal displacement of specific [125I]-insulin binding (IC50: Epi = 0.32 nM +/- 0.07 nM, Fib = 0.31 nM +/- 0.05 nM). Comparison of IGF-I (0.02 nM) binding to receptor preparations from epithelial and fiber cells demonstrated that specific binding was similar in the two preparations (Epi = 0.50 +/- 0.05 fmol, Fib = 0.42 +/- 0.05 fmol). Also, there was no difference in the concentration of IGF-I necessary for half maximal displacement of specific [125I]-IGF-I binding (IC50 = Epi: 0.27 +/- 0.05 nM, Fib: 0.28 +/- 0.04 nM). The ability of IGF-I to displace bound [125I]-insulin was also examined. The IC50 for IGF-I binding to the insulin receptors isolated from epithelial and fiber cells was 37.4 +/- 2.4 nM, and 35.4 +/- 2.8 nM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Human recombinant bFGF stimulates corneal endothelial wound healing in rabbits.

We have previously shown that bovine, human placenta extracted and recombinant human basic Fibroblast Growth Factor (bFGF) are effective in enhancing corneal epithelial wound healing in vivo. In the present study, we investigated the effect of rh-bFGF on the regeneration of injured rabbit endothelium. A standardized wound was created by scraping of endothelial cells with a special device within the boundaries of a central epithelial trephine mark of 7 mm in diameter. A single dose of 1.5 micrograms rh-bFGF was injected into the anterior chamber immediately after wounding, while control eyes received the vehicle only (n = 27). Functional recovery and wound closure rates were assessed by means of ultrasonic pachymetry, corneal button wet weight, endothelial vital staining as well as direct computer assisted surface analysis of Janus green stained corneal buttons. Measurements were carried out 1, 2, 4, and 7 days after injury. Morphological evaluation and cell counts at D4 and D7 were also performed. Significant stimulation of endothelial regeneration in rh-bFGF treated eyes, was observed with all methodological approaches. These results demonstrate the effectiveness of rh-bFGF in enhancing experimental corneal endothelial wound healing and advocate for a possible clinical application of this growth factor in order to preserve endothelial cell function or to promote healing of this important monolayer in case of disease or injury.


Partial purification and characterization of arylamine N-acetyltransferase in bovine retina.

Arylamine N-acetyltransferase (NAT) activity was partially purified and characterized in bovine retina. Upon examining the retinal supernatant for multiple ionic species, only one NAT activity was detected. Based upon its substrate specificity, it is best described as an arylamine NAT. According to size-exclusion HPLC, the molecular mass of the arylamine NAT is approximately 30-kDa. This arylamine NAT acetylates p-aminobenzoic acid thereby demonstrating a monomorphic pattern of acetylation. The NAT activity demonstrated low sensitivity to methotrexate inhibition as indicated by a high IC50 value (480 microM).


The rod sensitivity of dark adapted human infants.

The determinants of infants' low scotopic visual sensitivity are controversial. Some interpret infants' scotopic vision as indicative of immature rod photoreceptor function while others attribute infantile sensitivities mainly to post receptoral immaturities. To date the rod photoreceptor sensitivity of human infants has not actually been measured. In the work reported herein, electroretinographic a-wave responses, which represent the rod photoresponse, were recorded from dark adapted 10-week old infants and adult control subjects. Rod isolated a-waves indicate that 10-week-old infants' rods are less sensitive than adults'. Thus, any explanation of infants' scotopic visual sensitivity must take into account this fundamental property of infants' rods, low sensitivity.


Identification of alpha-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor.

The aqueous humor of the eye contains factors that regulate immunological responses within the immunosuppressive ocular microenvironment. Besides TGF-beta, the proteins in the low molecular weight (< 3500 Da) fraction of normal aqueous humor are also immunosuppressive. The low molecular weight fraction of aqueous humor inhibits IFN-gamma production and proliferation of antigen-stimulated lymph node cells. Neuropeptides are one possible family of low molecular weight factors in aqueous humor. Through the utilization of an antigen capturing enzyme-assay, the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) was detected in normal aqueous humor of humans, rabbits, and mice. The mean concentration of alpha-MSH in normal aqueous humor of humans was 20 +/- 3 pM, of rabbits 11 +/- 1 pM, of BALB/c mice 16 +/- 3 pM, and of C57BL/6 mice 14 +/- 3 pM. These physiological concentrations of alpha-MSH inhibited the production of IFN-gamma by antigen-stimulated lymph node cells. In contrast to the low molecular weight fraction, alpha-MSH did not inhibit proliferation. There was a 26% recovery of IFN-gamma production when alpha-MSH was absorbed from the low molecular weight fraction. The results demonstrate neuropeptides to be constitutive components of normal aqueous humor and that factors with the capability of differential regulation of effector T-cell activity may be present within the immunosuppressive ocular microenvironment.


Characterization and pathogenic potential of a soil isolate and an ocular isolate of Acanthamoeba castellanii in relation to Acanthamoeba keratitis.

Acanthamoeba castellanii, one isolate from the eye and one from the soil, were compared on the basis of: (a) pathogenic potential; (b) plasminogen activator activity; (c) chemotactic activity; (d) cytopathic effects; (e) collagenolytic activity; (f) binding ability to contact lenses; and (g) and binding ability to corneal buttons. The ocular isolate of A. castellanii was found to be pathogenic based on its ability to produce corneal infections in Chinese hamsters. By contrast, the soil isolate produced only mild lesions in a single Chinese hamster. Amoebae from the ocular isolate bound to corneal epithelium in greater numbers than the soil isolate counterparts. Moreover, ocular isolate organisms displayed plasminogen activator activity that was not detected in cultures from soil isolates of A. castellanii. Although neither the soil isolate nor the ocular isolate amoebae responded chemotactically to epithelial or stromal components, the ocular isolate displayed a curious and reproducible positive chemotactic response to endothelial extracts. Both A. castellanii isolates produced cytopathic effects on pig corneal epithelium, however the cytotoxicity from the ocular isolate was significantly greater than that of the soil isolate. The results indicate that the pathogenic potential of A. castellanii is correlated with the parasite's capacity to bind to corneal epithelium, respond chemotactically to corneal endothelial extracts, elaborate plasminogen activators, and produce cytopathic effects on corneal epithelium.


Confirmation of the role of pneumolysin in ocular infections with Streptococcus pneumoniae.

In earlier experiments on the role of the cytolytic toxin pneumolysin in ocular infections with pneumococcus, we found that a strain carrying a deletion in the gene encoding pneumolysin was considerably less virulent than wild type when tested in an intracorneal model of keratitis in the rabbit. To confirm this result, we have constructed a strain in which pneumolysin activity was restored by transformation of the deleted strain with a plasmid bearing the complete pneumolysin gene. Hemolytic titers of pneumolysin indicated that only one copy of the plasmid per bacterium expresses the pneumolysin gene in this strain. The virulence of this strain was compared with that of wild type and deleted strains transformed with the vector lacking the pneumolysin gene. Slit lamp examination (SLE) scores for eyes infected with the restored strain were similar to those for eyes infected with wild type and significantly greater than those for the pneumolysin-deleted strain. Molecular analysis of bacteria recovered from infected corneas showed that the vector plasmid was retained; however, in most isolates of the restored strain, the plasmid underwent an excision and lost the pneumolysin gene. The cloned gene apparently persisted long enough to induce the pathologic changes, and the results confirm the importance of pneumolysin as a virulence factor in ocular infections.


Mitochondrial dynamics in differentiating fiber cells of the mammalian lens.

The distribution of mitochondria was investigated in living rat and monkey lenses using rhodamine 123 staining and confocal microscopy. In both species, epithelial cells contained abundant small mitochondria scattered throughout the cell volume. Mid-sagittal slices of the living monkey lens revealed that, at the lens equator, mitochondria were only present in fiber cells to a depth of approximately 100 microns. Mitochondria were not present in fiber cells that had already reached the suture line or fibers abutting the central epithelium. Dual-staining with rhodamine 123 and the vital nuclear stain thiazole orange revealed that the loss of nuclei and mitochondria was coincident during fiber cell differentiation.


Report on the sequence of DQB1*0301 gene in ocular cicatricial pemphigoid patients.

Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affects the conjunctiva and other mucous membranes. Major histocompatibility complex (MHC) class II genes are important in autoimmunity because the antigen is presented to the T cell receptor in association with these molecules. A highly statistically significant association has been observed between patients with OCP and DQw7 (DQB1*0301) gene. DNA sequences of the second and third exons of the DQB1*0301 gene were determined in three OCP patients and compared with a control homozygous cell line for DQw7 from the Tenth International Histocompatibility Workshop. The sequences were identical in the patients studied and reference cell line. This data indicates that DQB1*0301 may only partly provide the enhanced susceptibility to get OCP and that another gene(s) in linkage disequilibrium with it and other factors may play an important role in the pathogenesis.


Protein analysis of monkey aqueous humor.

Aqueous humor from individual eyes of young monkeys (Macaca mulatta) was analyzed by gel exclusion chromatography, and one- and two-dimensional gel electrophoresis. The data indicated that in young normal monkey the main peak of protein eluting from gel exclusion columns was observed around 80,000 daltons. There was a small amount of heavy molecular weight material eluting from these columns with an apparent molecular size of greater than 500,000 daltons, but very little material smaller than 40,000 daltons. By one- and two-dimensional gel electrophoresis, the major polypeptide components in the monkey aqueous were similar to those reported for the human aqueous with polypeptides at around 170, 130, 110, 80, 67, 60, 42, 34, 28, 25, 22, 16, and 14 kilodaltons (kD). The monkey aqueous humor also contains the protease inhibitor cystatin.


Rearrangement and expression of immunoglobulin genes in transgenic mice.

Transgenic mice are discussed which carry a rearrangement test transgene. The methylation status of the transgene varies, depending on the background mouse strain. When the transgene is bred into the C57BL/6 strain, it is completely methylated and not rearranged in lymphoid organs. After several generations of crossing into DBA/2 or SJL the transgene becomes unmethylated and rearranges at high frequency. A strain specific modifier of DNA methylation (Ssm-1) was mapped close to the Friend virus susceptibility locus (Fv-1) on mouse chromosome 4. Rearranged transgenes from spleen, bone marrow and thymus of adult mice or fetal liver were cloned and sequenced. A great variety of joints was found, with about 1/3 being in the correct reading frame. Small deletions into the V- and J-coding ends as well as N region additions contributed to the variability. The fetal joints showed no N regions. Since no functional immunoglobulin (Ig) gene can be created from this artificial test gene, the data indicate that the rearrangement mechanism of the fetus differs from that of the adult.


Circulating peripheral blood plasma cells in multiple myeloma.

These studies indicate that monoclonal plasma cells can be detected in the peripheral blood of patients with active myeloma even when they are not detectable by routine WBC differentials performed on Wright-stained blood smears. These cells are usually not present in patients with MGUS and true SMM. They are detected in approximately 60% of patients with new, active MM and over 90% of patients with relapsed or refractory MM. If treatment is effective, they tend to decrease or disappear from the blood. When immunological, molecular, or cytogenetic studies are performed on peripheral blood cells from patients with MM, it must be realized that monoclonal plasma cells may be present and that they can influence the results of these tests. Although monoclonal plasma cells can circulate in the peripheral blood, it is not yet clear whether this cell represents the myeloma stem cell. It is possible that there are precursor cells that do not have plasma cell morphology in the blood or marrow that then differentiate into plasma cells. This question can only be answered by first depleting the plasma cells and then examining the remaining B-cells with appropriate immunological and molecular techniques.


Genes expressed selectively in plasmacytomas: markers of differentiation and transformation.

We have analyzed a murine plasmacytoma minus highly differentiated B lymphoma subtractive cDNA library and identified eight genes that are expressed in most plasmacytomas but at a much lower level, or not at all, in most B lymphomas. Four of the genes are markers of the terminal differentiation of B lymphocytes into plasma cells: placental alkaline phosphatase, also expressed in pre-B lymphomas xlr-3, a new X-linked member of the xlr multi-gene family EGP314, a pan-epithelial glycoprotein with sequence features of an adhesion molecule PC315, a gene that is up-regulated by IL6, but without obvious sequence homologies. Two of the genes are not clearly related to normal B cell differentiation, appearing to be associated with malignant transformation of plasma cells: PC326 is a new member of the beta-transducin mosaic protein gene family. It is an X-linked gene, expressed at a very low level in testis, but in no other normal tissue, including LPS- or IL6-induced plasma cells. It has a high level of expression (apparently dysregulated) in most (> 85%) mineral oil induced plasmacytomas. However the likelihood that PC326 is expressed decreases as the tumor latency decreases when different retroviral agents are used to accelerate mineral oil induced plasmacytomagenesis. This suggests that PC326 expression may be a late event in a multi-step process of tumorigenesis. PC251 a new member of the hematopoietic growth factor receptor family, most homologous to IL5R alpha.(ABSTRACT TRUNCATED AT 250 WORDS)


An exceptional mouse plasmacytoma with a new kappa/N-myc [T(6; 12) (C1; B)] translocation expresses N-myc but not c-myc.

Mouse plasmacytomas (MPC) carry one of three reciprocal translocations that juxtapose c-myc to one of the three immunoglobulin (Ig) loci. Here we describe an exceptional MPC, induced by pristane oil and Abelson (A-MuLV) virus. It does not carry any of the three c-myc/Ig translocations, but contains a previously unknown reciprocal T(6;12) translocation affecting the bands known to carry the IgK (6C/1) and N-myc (12B) loci, respectively. Northern blot analysis showed high N-myc but no c-myc expression. This is consistent with the constitutive activation of N-myc by a juxtaposition of the IgK and N-myc loci. Reciprocal translocation in B-cell derived tumors are believed to involve the Ig loci by the action of some enzyme that participates in the physiological rearrangement of the Ig loci. Only transcriptionally active chromatin regions are accessible to such recombinases (Alt et al. 1987). N-myc is not expressed in B-cells, but it is transcriptionally active during the early pro- and pre-B cell stage, whereafter it and the surrounding chromatin region becomes inactive (Smith et al. 1992). It is therefore most likely that the N-myc/Kappa translocation has arisen at an early stage of B-cell differentiation. This would imply that the myc/Ig translocations do not block B-cell differentiation. They also reaffirm the functional equivalence of N- and c-myc in relation to B-cell carcinogenesis, as shown by our previous work on tumor induction in N-myc transgenic mice (Wang et al. 1992).


Does HIV infection of B lymphocytes initiate AIDS lymphoma? Detection by PCR of viral sequences in lymphoma tissue.

Individuals infected with HIV (Human Immunodeficiency Virus) frequently develop B cell non-Hodgkins lymphoma. Although previous studies have failed to document the presence of HIV sequences in these tumors, the recent demonstration of malignant transformation of primary B lymphocytes by HIV-1 has prompted us to reinvestigate this issue. We have examined DNA extracted from 7 lymphomas and 5 lymphadenopathy specimens for HIV LTR (long terminal repeat), gag, and tat sequences using the polymerase chain reaction (PCR). All samples produced products of the expected size with primers for these regions, indicating the presence of HIV proviral sequences in these tissues. The amount of provirus in the tissue was estimated by normalizing the amount of HIV product to the amount of product for the cellular myc gene or beta globin gene. Products were quantitated during the exponential phase of DNA accumulation. These studies indicated that provirus was present at approximately one copy per cell in the 7 lymphoma samples and in 4 of the 5 lymphadenopathy samples. These results are consistent with a direct role for virus in the initiation of lymphoma. Studies to determine whether provirus resides in the lymphoma cells per se will be necessary to further substantiate this hypothesis.


Transcriptional activities of the Myc and Max proteins in mammalian cells.

The myc family of oncogenes exhibit deregulated expression in a host of neoplasias. Though the molecular function of the Myc protein in both normal and tumorigenic cells has remained uncertain, it has been postulated to play a role in gene transcription on the basis of amino acid homologies with known transcription factors such as MyoD (Lüscher & Eisenman, 1990). We report here the direct testing of full-length Myc and its dimerization partner, Max, on the transcriptional activity of reporter genes bearing Myc/Max binding sites. Such reporter constructs display an endogenous level of activity in transient transfections which is dependent on the presence of the CACGTG sequence. Exogenous expression of myc results in modest activation of reporter gene transcription. Similar overexpression of max results in a repression of reporter gene activity, an effect which is reversed by co-expression with c-myc. Max repression is dependent on an intact DNA binding region, while Myc activation depends on both the N-terminal activation and the C-terminal dimerization domains. These results suggest a model in which Max homodimers can act as as repressors, and Myc-Max heterodimers as activators, of potential target genes.


Loss of p53 expression in Myc-induced B lineage tumors.

Tumors are formed following the accumulation of several genetic changes in genes which normally function to regulate cell growth. As yet it is unclear why multiple mutations are required, which type of alterations can collaborate with each other, and if collaboration is cell-type specific. In our myc transgenic mouse model system both point mutations and loss of mRNA expression for the p53 tumor suppressor gene have been found in the myc-induced B-lineage tumors arising spontaneously in these mice. This demonstrates the collaboration between these two growth control genes in cellular transformation. The observation that alterations in the expression of p53 is a common phenomenon in tumors formed in myc transgenic mice as well as a variety of different types of human tumors suggests that inactivation of the p53 growth control pathway may be required for transformation, and that alterations in p53 itself might be the most efficient way to achieve this inactivation. An analysis of the molecular mechanism for p53 alterations has implications for what kind of factors, both environmental and physiological, can influence tumor formation. The identification of collaboration groups has implications for the process of tumor formation, growth regulation, and will some day be important for the diagnosis of cancer, the prognosis of the individual and the design of specific therapeutic agents for treatment.


The purification of B-cell precursors from mouse fetal liver.

Lymphocyte progenitor cells isolated on sequential days of gestation from mouse fetal liver represent distinct stages in B cell development. We have utilized polymerase chain reaction (PCR)-based assays to detect immunoglobulin (Ig) gene rearrangement and flow cytometry to assay cell surface markers following fractionation based on the differential expression of the B cell-specific phosphatase CD45 (B220). The purification of B220+ cells from day 17 fetal liver resulted in a 10-fold enrichment of cells which had undergone gene rearrangement events. We have also shown that day 13 fetal liver cells activate successive Ig gene rearrangements during short-term culture in the presence of fetal calf serum (FCS), interleukin-3 (IL3), and interleukin-7 (IL7). However, partially purified lymphocyte precursors fail to activate Ig gene rearrangement in culture unless they are cultured in the presence of a stromal cell line.


Pediatric limb amputation: aspects of coping and psychotherapeutic intervention.

This paper addresses the assessment of and intervention with pediatric patients undergoing limb amputation. A multicomponent treatment package is advocated including the use of play and cognitive-behavioral strategies to enhance coping and adjustment to the loss of a limb.


Special education placements of language-disordered children in a psychiatric population.

Children evaluated by an interdisciplinary team that provided data on psychiatric disturbance, language handicaps, and psychoeducational assessment were placed in special education classes following the complete evaluation. Discriminant analysis as a special case of multiple regression analysis determined that mean reading achievement score, pre-evaluation classroom placement, and to a lesser degree, Performance IQ predicted classroom placement. Overall, correct classroom predictions approached 90 percent. These findings highlight the value of interdisciplinary evaluation to educators and mental health professionals.


Sexuality in traditional China: its relationship to child abuse.

The sexual and marital history of China for 3000 year is reviewed, indicating a general open humanistic attitude about sex, with little perversion, sado-masochism, or denigration of sexuality. Foot fetishism (particularly foot binding) has been extensive in the past, but less so since World War I. Respect for women and their sexual rights and importance has been related to the low rate of child abuse. Currently, restrictions on sexual freedom and psychological injury to children is increasing in the urban areas (20% of the population) with resultant increase in infanticide particularly of little girls.


Cluster analysis of child behavior checklists of 6 to 11-year-old males with varying degrees of behavior disorders.

Achenbach Child Behavior Checklist ratings were collected on boys aged 6 to 11 years screened as not having significant behavior problems, as clinic-referred boys, and as boys diagnosed as having Attention Deficit-Hyperactivity Disorder alone or together with Oppositional-Defiant Disorder or Conduct Disorder. Cluster analysis resulted in a classification system related to DSM-III-R classification of the boys and parent self-report of mildly antisocial acts. Clusters also enhanced the ability of the instrument to detect Attention Deficit Hyperactivity Disorder and disruptive behavior disorders.


Comorbidity for disruptive behavior disorders in psychiatrically hospitalized children.

A variety of instruments were used to compare six groups of inpatient children: pure attention deficit disorder with hyperactivity (ADDH), pure conduct disorder (CD), pure oppositional defiant disorder (OD), ADDH + CD, and ADDH + OD, and a clinical control group who had no DBD diagnosis. Children with ADDH and CD or OD exhibited a greater degree of psychopathology. Children with CD and OD were more similar than different, indicating that perhaps a continuum of pathology exists between these diagnostic classifications.


Behavior problems in sons and daughters of substance abusing parents.

Information to address the question of whether sex specific features exist in behavioral characteristics of children of substance abusing parents was gathered from the records of a large number of hospital treated youth. There was a trend for sons of substance abusing parents to have more conduct disorder diagnoses in association with severe aggressive/destructive behavior than sons of non substance abusing parents. Girls of substance abusing parents generally were more likely to have attention deficit/hyperactive, aggressive and conduct disorder problems than girls of non substance abusing parents.


[Preoperative risk assessment with the ASA classification. A prospective study of morbidity and mortality in various ASA classes in 2,937 patients in general surgery].

The value of ASA classification in assessment of perioperative risk, i.e. especially postoperative morbidity, was analyzed prospectively using the data of 2937 patients. The analysis took into account the criteria validity, reliability, and sensitivity. The incidence of post-operative morbidity after elective surgery rose from 3.9% in ASA class I to 36% in ASA class IV. Mortality was 0.6% in ASA class II, whereas 9.3% died in ASA class IV. Morbidity, mortality respectively, after emergency surgery was 10.2% in ASA class II compared to 69% in class IV, mortality 1.4% compared to 21.5%. Differences between the ASA classes were confirmed (p-value < 0.05) considering separate kinds of complications and different periods. Furthermore, ASA classification was a valuable reference to length of stay and severity of necessary therapy at the ICU.


[Differential surgical therapy in diffuse peritonitis].

96 patients were operated on for diffuse peritonitis from January 1986 to June 1990. They underwent a differentiated therapeutical concept according to the severity of the underlying peritonitis. Mild forms were handled with the standard approach, while mid-severe cases were treated by continuous postoperative peritoneal lavage. Patients with severe peritonitis were operated on by open abdomen management. Mortality was 32% (31/96) and with that obviously better than the statistically expected mortality, based on the Mannheim-Peritonitis-Score (49%). The same findings could be demonstrated in the therapeutic subgroups. The management of diffuse peritonitis using such a differentiated surgical concept seems to be an effective approach to reduce mortality rates.


[What is the cost of laparoscopic cholecystectomy?].

After laparoscopic cholecystectomy (LC) has replaced open cholecystectomy (OC) to a large extent as standard method in the operative treatment of cholecystolithiasis the question of costs and economics raises. To evaluate this question the data of 50 patients who underwent elective LC were analysed in a retrospective study and compared with the data of 50 patients who were cholecystectomized using the open technique. The median of in-hospital stay was 6 (3-15) days for LC and 10 (3-33) days for OC. The median of time of working-disability was 14 (2-35) days for LC and 21 (2-56) days for OC. Total cost (median) of 3788 (2637-8101) DM for LC compared to 4509 (2041-15218) DM for OC. The median of hospital income was 2790 (1395-6975) DM for the LC-group and 4650 (1395-15346) DM for the OC-group. Due to the shorter in-hospital stay of LC-patients this method causes a microeconomical loss for the hospital compared to OC. Macroeconomically LC represents a benefit because of shorter working-disability.


[Thoracoscopic middle lobe resection].

The authors report a case of middle lobectomy by a thoracoscopic procedure. A forty-year old patient had carcinoma of the middle lobe (6 cm diameter). The use of staplers and ligatures by this way allows the control of the different vessels and bronchus. The indications of that technique must be evaluated in the future.


[Argon gas embolism in laparoscopic cholecystectomy with the Argon Beam One coagulator].

The report is about argon embolism in a 37-year-old female patient during laparoscopic cholecystectomy and coagulation of a liver bed bleeding with the "Argon Beam One". The presented case report is to show that in spite of technical perfection and correct use of the Argon Beam One coagulator unfavorable anatomical conditions can cause life threatening gas embolism.


Intestinal absorption of aluminium.

The intestinal absorption of aluminium can contribute significantly to systemic exposure to this element. Aluminium can be absorbed not only from oral pharmaceuticals but also from solid food and drinking water. The absorption process is not restricted to patients with kidney disorders; other groups of patients and healthy subjects are not excluded. Details of the absorptive mechanism are mainly obtained from in vitro (everted gut sac) and animal studies (intestinal perfusion) rather than from controlled human studies and case reports. The process of absorption depends on the intraluminal speciation, the intraluminal quantity, the presence of competing (iron, calcium) or complexing (citrate) substances and the intraluminal pH. The condition of the exposed organism with respect to the gut also determines intestinal absorption (iron status, calcium [vitamin D, parathyroid hormone] status, age and kidney function). Various absorption sites and passage routes, both transcellular and paracellular, have been reported, each apparently related to a different aluminium species (hydrated ionic species, aluminium citrate complex etc.). No uniform mechanistic model allowing extrapolation to the clinical situation has yet emerged.


Aluminium intoxication in renal disease.

Aluminium intoxication in renal failure occurred over weeks or months when dialysis fluid or parenteral solutions were heavily contaminated and over many years when the main source was oral administration of aluminium-containing phosphate binders. Encephalopathy was common during subacute intoxication but in slow aluminium poisoning the main brunt was borne by the bones. However, in both tempos of intoxication several organs or systems were involved. Encephalopathy was usually accompanied by bone disease, bone disease by parathyroid suppression and both by anaemia. The heart and the lymphocytes are probably damaged by aluminium overload. Among the many questions left unanswered 15 years after the incrimination of aluminium as the cause of this multi-system illness are: (1) does low level aluminium overload in renal failure cause gradual deterioration in cerebral function? And, if so, (2) does it resemble Alzheimer's disease or a slow-onset version of dialysis encephalopathy? The evidence we review suggests that the answer to (1) is 'yes' and to (2) 'probably the latter'.


Aluminium and Alzheimer's disease.

The hypothesis that aluminium (Al) is a cause of (or a risk factor in) the development of beta-amyloid plaques and neurofibrillary tangles (NFT) and dementia in Alzheimer's disease (AD) is based on studies by Wisniewski et al, Klatzo et al and Terry & Peña in 1965 that showed that injection of experimental animals with Al compounds induces the formation of NFT. Other publications revealed that Al affects cognitive functions in experimental animals and humans undergoing dialysis for renal failure. Electron probe and laser microprobe mass analysis (LAMMA) studies have demonstrated the presence of Al in NFT and cores of amyloid stars and nuclei of neurons in AD patients. Other studies have indicated the association between amyotrophic lateral sclerosis/Guam parkinsonism-dementia complex and Al in the environment. A recent report suggests that the chelating agent desferrioxamine slows the rate of cognitive decline in AD patients. Extensive studies of the pathology of AD and Al-induced encephalopathy by our group and others indicate that Al does not cause Alzheimer's disease neuropathology. However, under certain conditions, cognition can be affected when Al enters the brain. Therefore, for individuals with renal failure or undergoing dialysis or individuals with a damaged blood-brain barrier, the intake of Al should be controlled.


Aluminium accumulation, beta-amyloid deposition and neurofibrillary changes in the central nervous system.

Deposition of beta-amyloid and the formation of neurofibrillary tangles (NFTs) are central to the aetiopathogenesis of Alzheimer's disease (AD). The possible effects of aluminium on these processes have been investigated in patients with renal failure who are exposed chronically to high blood levels of aluminium. Focal accumulation of aluminium was observed in neurons with high densities of transferrin receptors, indicating transferrin-mediated uptake, in regions such as cortex and hippocampus which are selectively vulnerable in AD. Increased staining for the beta-amyloid precursor protein (APP) in cortical pyramidal neurons was evident in the majority of renal patients and immature senile plaques were present in 30% of cases, suggesting that aluminium may induce or accelerate beta-amyloid deposition. The absence of neurofibrillary changes in this group of renal patients indicates that aluminium does not directly cause the formation of NFTs. The brain aluminium content was not raised in neuropathologically assessed cases of AD and we have been unable to confirm claims of defective transferrin binding in this disorder. If aluminium contributes to the development of sporadic AD, it must do so indirectly, perhaps via effects on the synthesis or metabolism of APP, or by contributing generally to the age-related attrition of neurons and thus reducing the threshold for deficits produced by more specific disease-related processes.


Elemental analysis of neurofibrillary tangles in Alzheimer's disease using proton-induced X-ray analysis.

We have investigated the elemental content of hippocampal slices from normal human brain and from brains of Alzheimer's disease patients by X-ray fluorescence using both electron and proton beam microprobes. The sections have been stained with a dye--toluidine blue--which contains sulphur so that the X-ray fluorescence map can be correlated with known intracellular sites as seen under the light microscope. The results show that associated with neurofibrillary tangles and Hirano bodies (the distinctive internal visual features of cells from Alzheimer's disease patients) there is increased calcium. We cannot confirm that there are peculiarities in the distribution of aluminium in cells.


Aluminium(III) in experimental cell pathology.

Controversy over the relevance of aluminium to certain human encephalopathies has emphasized the importance of in vivo and in vitro models as tools for shedding light on the biological and molecular aspects of the aluminium toxicity. The search for an experimental model in animals or in cultured cells able to reproduce specific pathological human conditions may prove to be an unattainable aim; nevertheless, in vivo and in vitro models should be actively sought and the pathological changes induced in experimental animals should always be evaluated at the cellular level, just as for changes produced directly in cultured cells. These toxicological aspects are outlined with particular emphasis on the role played by the molecular form of aluminium (metal speciation) in determining the quality and intensity of the metal's biological effects.


Aluminium and the neurofibrillary tangle: results of tissue microprobe studies.

Despite the contradictory results of studies attempting to compare the bulk brain tissue aluminium content of specimens from Alzheimer's disease patients and controls, microprobe studies from our laboratory have consistently documented evidence of selective accumulation of the element within the neurofibrillary tangle-bearing cells associated with this condition. Laser microprobe mass analysis (a highly sensitive and precise technique for trace elemental microprobe analysis) has now demonstrated that the most prominent aluminium accumulations occur within the neurofibrillary tangle itself. Similar findings have been obtained from microprobe studies of the neurofibrillary tangles which are a characteristic feature of amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. Although the intraneuronal localization of aluminium in the Guam-derived specimens is similar to that of Alzheimer's disease, the concentration of aluminium is considerably higher than is encountered in Alzheimer's disease specimens. We conclude that aluminium is an integral component of the neurofibrillary tangle and raise the possibility that the cross-linking properties of this highly reactive metal may stabilize the constituent cytoskeletal proteins which make up this pathological structure.


Dietary and other sources of aluminium intake.

Aluminium in the food supply comes from natural sources including water, food additives, and contamination by aluminium utensils and containers. Most unprocessed foods, except for certain herbs and tea leaves, contain low (< 5 micrograms Al/g) levels of aluminium. Thus most adults consume 1-10 mg aluminium daily from natural sources. Cooking in aluminium containers often results in statistically significant, but not practically important, increases in the aluminium content of foods. Intake of aluminium from food additives varies greatly (0 to 95 mg Al daily) among residents in North America, with the median intake for adults being about 24 mg daily. Generally, the intake of aluminium from foods is less than 1% of that consumed by individuals using aluminium-containing pharmaceuticals. Currently the real scientific question is not the amount of aluminium in foods but the availability of the aluminium in foods and the sensitivity of some population groups to aluminium. Several dietary factors, including citrate, may affect the absorption of aluminium. Aluminium contamination of soy-based formulae when fed to premature infants with impaired kidney function and aluminium contamination of components of parenteral solutions (i.e. albumin, calcium and phosphorus salts) are of concern.


Molecular characterization and measurement of Alzheimer's disease pathology: implications for genetic and environmental aetiology.

The neuropathological changes seen in Alzheimer's disease represent an interaction between the ageing process in which normal intellectual function is retained, and changes which are specifically associated with severe cognitive deterioration. Molecular analysis of these changes has tended to emphasize the distinction between neurofibrillary pathology, which is intracellular and highly correlated with cognitive deterioration, and the changes associated with the deposition of extracellular amyloid, which appears to be widespread in normal ageing. Extracellular amyloid deposits consist of fibrils composed of a short 42 amino acid peptide (beta/A4) derived by abnormal proteolysis from a much larger precursor molecule (APP). The recent demonstration of a mutation associated with APP in rare cases with familial dementia, neurofibrillary pathology in the hippocampus and atypical cortical Lewy body pathology raises the possibility that abnormal processing of APP could be linked directly with neurofibrillary pathology. Neurofibrillary tangles and neuritic plaques are sites of dense accumulation of pathological paired helical filaments (PHFs) which are composed in part of an antigenically modified form of the microtubule-associated protein tau. The average brain tissue content of PHFs measured biochemically does not increase in the course of normal ageing but increases 10-fold relative to age-matched controls in patients with Alzheimer's disease. There is also a substantial (three-fold) disease-related decline in normal soluble tau protein relative to age-matched controls. This intracellular redistribution of a protein essential for microtubule stability in cortico-cortical association circuits may play an important part in the molecular pathogenesis of dementia in Alzheimer's disease. The role of abnormal proteolysis of APP in this process remains to be elucidated. Immunohistochemical studies on renal dialysis cases have failed to detect evidence of neurofibrillary pathology related to aluminium accumulation in brain tissue. Nevertheless it needs to be seen whether more sensitive biochemical assays of neurofibrillary pathology can demonstrate evidence of an association with aluminium.


Aluminium speciation in biology.

Before we can understand the role of Al3+ in living organisms we need to learn how it interacts with molecules found in biological systems. The only aluminium oxidation state in biology is 3+. In aqueous solutions there are only two main Al(III) species: the hexahydrate Al3+ at pH < 5.5 and the tetrahedral aluminate at pH > 6.2. In the blood plasma, citrate is the main small molecule carrier and transferrin the main protein carrier of Al3+. In fluids where the concentrations of these two ligands are low, nucleoside di- and triphosphates become Al3+ binders. Under these conditions Al3+ easily displaces Mg2+ from nucleotides. When all three classes of ligands are at low concentrations, catecholamines become likely Al3+ binders. Double-helical DNA binds Al3+ weakly and under no conditions should it compete with other ligands. Al(III) in the cell nucleus probably binds to nucleotides or phosphorylated proteins. Al3+ undergoes ligand exchange much more slowly than most metal ions: 10(5) times slower than Mg2+.


The interrelationship between silicon and aluminium in the biological effects of aluminium.

It is well established that aluminium is toxic at the cellular level and that pathological symptoms follow its entry into organisms (plants, fish, humans) when the normal exclusion mechanisms fail or are bypassed, as for example in renal dialysis. The present debate concerns the availability of environmental aluminium and the possible impact of its slow and insidious absorption and accumulation in vulnerable individuals. Silicon is considered as essential element but the mechanisms underlying its essentiality remain unknown and binding of the element (through oxygen) with biomolecules has not been demonstrated. There is, however, a unique affinity between aluminium and silicon, not only in solid state chemistry ([AlO4]5- and [SiO4]4- are isostructural), but also in aqueous solution chemistry as illustrated by the synthesis of zeolite from aluminate and silicate anions at high pH and under hydrothermal conditions. This affinity exists also in very dilute solution (< 10(-5) M) at near-neutral pH when hydroxyalumino-silicate species form. These species mediate the bioavailability and cellular toxicity of aluminium. The observed effects of silicon deficiency can be attributed to consequential aluminium availability. There are important implications for the epidemiology and biochemistry of aluminium-induced disorders and any consideration of one element must include the other.


The epidemiology of Alzheimer's disease in relation to aluminium.

The combination of an ageing population, an exponential increase in the incidence of dementing illness with age, and the high demands that demented patients place on health care resources makes Alzheimer's disease a major public health issue. So far, epidemiologists have made better progress in quantifying the frequency of the disease than in identifying strong risk factors, but evidence is accumulating to implicate environmental exposure to aluminium in the aetiology. The finding of a geographical correlation between death rates from dementia and water aluminium concentrations in Norway has since been replicated in several other surveys. Although ecological studies of this type should be interpreted cautiously, the association between Alzheimer's disease and aluminium in drinking water may prove to be an example of a potentially important biological effect of aluminium.


Aluminium and the pathogenesis of Alzheimer's disease: a summary of evidence.

Known risk factors for Alzheimer's disease (AD) are few and insufficient knowledge is available to recommend steps to reduce AD in our ageing populations. Although not 'the cause', considerable evidence implicates human ingestion of aluminium as a possible risk factor for the expression of dementia of the Alzheimer type. A recent epidemiological study in Ontario relating the incidence of AD to aluminium in drinking water strongly supports this conclusion. To test further the hypothesis that aluminium may play a role in the pathogenesis of AD we conducted a clinical trial employing the trivalent metal ion binding compound, desferrioxamine. The design was a two-year randomized trial with behavioural assessments blinded to study assignment. Sixty-three patients with probable AD were selected who were living at home and were under 74 years. Forty-eight signed an informed consent and completed all initial testing. The main outcome measure was a video-recorded home-behavioural assessment of measures of skills of daily living. The principal outcome was that the mean slope for performance of the skills of daily living for the group without treatment was -1.72% maximum score/month, compared to -0.87% maximum score/month for the group treated with desferrioxamine (P = 0.038). Considerable evidence supports the hypothesis that aluminium has an active role in the pathogenesis of AD.


Prevention of some types of inflammatory damage using AA 231-1, a fluorinated beta-lactam.

The leukocyte elastase inhibitory activity of AA 231-1, a suicide substrate, was investigated in the presence of elastin, a natural substrate of elastase, and its efficiency to reduce the degradation of basement membrane and haemorrhage induced by elastase was analysed. Elastin only moderately decreased the inhibitory efficiency of AA 231-1. The digestion by human leukocyte elastase (HLE) of glomerular basement membrane prepared from pig kidney was prevented in the presence of AA 231-1. Intradermal microvascular haemorrhage was also significantly inhibited by AA 231-1. These results suggest that AA 231-1 may be a valuable candidate as an anti-inflammatory agent.


Deficits in cholinergic neurotransmission markers induced by ethylcholine mustard aziridinium (AF64A) in the rat hippocampus: sensitivity to treatment with the monoamine oxidase-B inhibitor L-deprenyl.

Assessment was made of the effects of intracerebroventricular (i.c.v.) administration of ethylcholine mustard aziridinium (AF64A) and of the monoamine oxidase (MAO)-B inhibitor L-deprenyl on the acetylcholine (ACh) biosynthetic enzyme choline acetyltransferase (ChAT), on the ACh catabolic enzyme acetylcholinesterase (AChE) and on the density of ACh muscarinic M-1 and M-2 receptor sites. In addition, the effect of AF64A and of L-deprenyl treatment on the localization of AChE activity in the CA-1 and CA-3 fields of the hippocampus was evaluated by combined enzyme histochemistry and microdensitometry techniques. I.c.v. injection of AF64A induced, 4 weeks after administration of the neurotoxin, a remarkable increase of MAO-B activity, and a significant reduction of ChAT and AChE activities in the hippocampus but not in the neostriatum which was used as a reference tissue. Hippocampal muscarinic M-1 receptors were unaffected by AF64A administration, whereas M-2 sites were reduced after neurotoxin injection. Enzyme histochemistry analysis showed that the loss of AChE induced by AF64A was more pronounced in the CA-3 than in the CA-1 field of the hippocampus. Treatment with L-deprenyl induced, from a dose of 11.17 microM/kg/day, a significant reduction of MAO-B activity in the hippocampus. The expression of ChAT and AChE, as well as the density of M-2 receptors, was increased after L-deprenyl administration in the hippocampus but not in the neostriatum. An increase in AChE reactivity was noticeable in the CA-1 and CA-3 fields of the hippocampus of AF64A-injected rats treated with L-deprenyl.(ABSTRACT TRUNCATED AT 250 WORDS)


Recent findings on the regulatory functions of CoA and the normalizing activity on plasma lipids of exogenous CoA.

In recent years many studies have shown that coenzyme A (CoA) is not only an acyl carrier coenzyme but it also has an important role in the regulation of metabolic functions and cell activities such as transport from the Golgi cisternae. This regulatory role is carried out by CoA, its precursor, catabolites and acylated derivatives. The acylation (myristylation and palmitylation) process of peptides and proteins dependent on CoA seems to be an important regulatory mechanism of cell activities. Furthermore exogenous CoA has been shown to decrease the triacylglycerols, cholesterol and Apo B of plasma lipoproteins in man. This regulatory mechanism acts either on VLDL synthesis and secretion or on their plasma clearance. CoA also protects cell-membrane and plasma lipoproteins against the peroxidative action of oxygen free-radicals.


Sulodexide oral administration influences blood viscosity and fibrinolysis.

The aim of this study was to verify the effects of oral administration of a new enteric-coated formulation of sulodexide on blood viscosity and fibrinolysis. Six outpatients suffering from peripheral artery occlusive disease were administered orally two enteric-coated tablets containing 50 mg of sulodexide, twice daily for seven days. On the first and seventh administration days, the following parameters were evaluated: plasminogen activator inhibitor (PAI-1) activity, PAI-1 antigen, tissue plasminogen activator (t-PA) and whole blood, serum and plasma viscosity, before (0 time) and 2, 4 and 8 hours after ingestion of the drug. Following the first administration (50 mg), a slight reduction of PAI was registered; after 7 days' administration, a clear-cut lowering of functional and antigenic PAI was observed, together with an increase of t-PA. As to the drug's influence on blood viscosity, after 7 days the most evident reduction was that registered for plasma viscosity. No side effects were observed throughout the treatment period.


Aztreonam compared to chloramphenicol in the treatment of enteric fevers.

Fifty-seven patients, twenty-six males and thirty-one females, aged 6 to 50 years (mean 12.6 years) with proven Salmonella typhi or S. paratyphi A septicaemia, were treated in an open randomized parallel study with either aztreonam or chloramphenicol. Aztreonam was given intramuscularly at a level of 50 to 80 mg/kg body weight per dose every 8 h for 7 days to thirty patients. Chloramphenicol was given orally in a dose of 50 to 70 mg/kg body weight every 6 h for 12 days to twenty-seven patients. All patients responded rapidly to treatment, becoming afebrile and asymptomatic within 5.5 to 6.4 days. Only one patient on aztreonam relapsed following treatment, whereas three patients relapsed after chloramphenicol treatment. There were no serious side effects with either drug.


Clinical evaluation of a new NSAID applied topically (BPAA gel) vs. diclofenac emulgel in elderly osteoarthritic patients.

This study reports therapeutic results obtained with a group of elderly subjects suffering from osteoarthritis undergoing therapy with a new topically applied NSAID (BPAA gel). Excellent results, ease of use and absence of side effects are the essential characteristics of the anti-inflammatory drug in this preparation. Results were compared to those obtained in a homogeneous sample treated with diclofenac emulgel. No statistically significant differences were observed in therapeutic effectiveness.


How fast should the night shift rotate?

Claims are frequently made that changing from morning to afternoon to night shift at about two- to three-day intervals (rapid rotation) is the best way of organizing 24h staffing. A critical analysis is made of the grounds for these assertion, followed by a review of evidence bearing upon the issue of whether longer periods of rotation are to be preferred. The conclusion is that permanent (zero rotation), fixed-night systems are superior on most counts, and should be implemented for night work, leaving the option of rapid rotation to cover the two (morning and afternoon) day shifts. This said, the multiplicity of shift systems and settings means that this will not always be the method of choice. Furthermore the recommendation should be regarded as provisional pending a search for more data directly comparing the two systems.


How fast should the night shift rotate? A rejoinder.

The argument for greater use of permanent night shift does not match the three times greater use of rotating three-shift systems in Britain. Studies of industrial production show very slight differences between output on different shifts, unlike laboratory studies, suggesting that it is almost impossible to reproduce the practice, motivation, and real consequences of work in laboratory settings. People who prefer permanent night shift often prefer to avoid management, and few managements welcome this; or have important tasks to perform at home in the day-time. Some studies of adaptation have defined inversion of temperature curves poorly, and most night-workers never completely adapt. Social flexibility, which has been the main attraction of rapidly rotating shifts, can be reproduced on permanent night shifts, but then loses the possibility of adaptation.


Is there a 'best compromise' shift system?

In his review Wilkinson considers the question 'How fast should the night shift rotate? He concludes quite strongly that with the possible exception of social factors, most of the evidence favours the use of prolonged or permanent night shifts. In this reply I argue that in reaching this conclusion Wilkinson has (i) overestimated the problems associated with rapidly-rotating shift systems; and (ii) underestimated the problems that might be encountered in trying to implement effective permanent night shift systems. The evidence on the various problems reviewed by Wilkinson is reconsidered. Other aspects of shift systems that were ignored by Wilkinson are then also taken into account. It is concluded that the evidence does not allow a general choice to be made between the use of either permanent night shifts or rapidly rotating, delaying, shift system. Rather the choice between them would appear to depend on the relative importance attached to safety and social problems in any given workplace.


Ranges of dynamic motion of the wrist in healthy young and middle-aged men.

The difference in the range of dynamic motion of the wrist between young and middle-aged men was studied. To analyse wrist function easily, a new quantitative evaluation technique for wrist circumduction using a biaxial flexible electrogoniometer was introduced. A phase plane was made from two-channel signals of the electrogoniometer, and the 'ROM (range of motion) Index' for wrist circumduction was defined. Twelve healthy young men (age 19-31 years) and twelve healthy middle-aged men (age 45-63 years) were studied. Under forearm fixed conditions, there was no difference of the ROM Index between the two age groups. A significant decrease of the ROM Index in the middle-aged group was found in the non-dominant wrists without forearm fixation. The four quadrantal analysis of wrist circumduction clarified that this difference appeared especially in the radiodorsal direction. These results suggest that in the middle-aged men, the motor function involving the radiocarpal and midcarpal joints does not decrease, but that for the proximal and distal radioulnar joints in the non-dominant side drops.


Postsurgical follow-up by MRI of anterior cervical discectomy without fusion.

Postoperative magnetic resonance imaging (MRI) findings are described in selected patients with cervical radiculopathy and a cervical soft disc herniation, treated by anterior cervical discectomy (ACD) without fusion. Six months postoperatively, 45 patients underwent MRI examination using a 0.5 T superconductive unit. T1- and T2-weighted spin echo sequences were acquired on sagittal and axial planes. A low signal intensity on T2-weighted images was visualized at the ACD level in all patients. Five patients were found to have a slight kyphosis at the discectomy level. There was no residual disc material at any ACD level. In 5 patients, areas of diminished signal intensity on T1- and T2-weighted images on adjacent vertebrae was noticed, indicating sclerosis of the cortical bone adjacent to the ACD level. In 3 patients, cervical disc protrusions without impression on the dura were visualized postoperatively: 2 below and 1 above the ACD level. One patient developed a cervical disc herniation without complaints one level above the operated one. No patient developed infolding or degenerative swelling of the ligamenta flava and no intrinsic cord abnormalities were present. MRI provided useful information on pathology, allowing a non-invasive evaluation following ACD and enabling a better understanding of surgical consequences.


Bone scans in patients with osteoarthritis of the hip for the evaluation of bipolar hip arthroplasty: quantitative analysis using SPECT.

To establish the time-course of bone scans after bipolar hip arthroplasty (BHA) bone scanning was performed before and after surgery in 22 hips. The influence of migration of the outer head into the acetabulum on the time-course of bone scans was examined by analyzing the relationship between the uptake of radioisotope and the magnitude of migration. The bone scans were quantitatively analyzed by single photon emission computed tomography (SPECT) on the basis of the ratio of radioactivity at the acetabulum to that in the anterior superior iliac spine (ASIS). The increased radionuclide activity decreased exponentially to a baseline with time after surgery. The postoperative uptake ratio could be expressed as a function of the preoperative uptake ratio and the postoperative length of time. The regression slope representing the decreasing rate of uptake showed no significant differences between two groups divided by the magnitude of migration of the outer head. Migration of the outer head was considered not to influence the time-course of the bone scans.


Use of percutaneous nephrostomy in hydronephrosis of pregnancy.

Traditional methods of urinary diversion in pregnancy include retrograde passage of ureteral catheter or stents and operative nephrostomy. These techniques are, however, associated with the use of anesthesia, are technically difficult to perform, and may induce labor. We report the use of percutaneous nephrostomy in four pregnant patients, two with obstruction due to ureteral calculi and two with infected hydronephrosis. The procedure provided rapid relief from pain and pyosepsis, and allowed uneventful continuation of the pregnancy to full-term, with preservation of renal function.


Spiral versus conventional CT in soft tissue diagnosis.

Spiral volumetric computed tomography (SVCT) has been predicted to improve vascular and organ enhancement with little effect on image quality. To see if this was the case, we studied 100 patients referred for computed tomography where we would normally have performed dynamic incremental computed tomography (DICT). Patients were randomly allocated to undergo either standard DICT or SVCT. The resulting images were analysed for overall quality, the degree of contrast medium enhancement and the extent of artefacts associated with the technique. No statistically significant difference in overall image quality between SVCT and DICT was found, apart from images of the hepatic parenchyma where the quality was significantly worse on SVCT (P < 0.05) due to the low mA permissible. Contrast enhancement was better with SVCT, although only for the thorax (P < 0.01) and the group taken as a whole (P < 0.01) did this improvement reach statistical significance. There was no statistically significant difference between the extent of artefacts observed in the two techniques. As expected, all acquisition times were shorter using SVCT. The benefits of SVCT have been well described and include the absolute contiguity of the reconstructed images and the ability to obtain many images at peak contrast enhancement. We have confirmed the latter effect. We are now also satisfied that there is no appreciable loss of overall image quality except where large volumes of solid tissue are being examined (e.g. liver).


Imaging techniques in myotonic dystrophy. A comparative study of ultrasound, computed tomography and magnetic resonance imaging of skeletal muscles.

Limb and trunk muscles of 57 patients with the juvenile or adult form of myotonic dystrophy were studied by imaging techniques (ultrasound, computed tomography, magnetic resonance imaging). Typical findings were atrophy of the tibialis anterior and triceps brachii muscles and fatty degeneration of the vastus intermedius, sartorius, tibialis anterior and soleus muscles as well as of medial head of the gastrocnemius muscle. Magnetic resonance imaging was the most sensitive technique in depicting mesenchymal muscle alterations, followed by computed tomography and ultrasound. The data support that imaging is more sensitive in detecting the myopathy than measurement of the creatine kinase activity.


Digital subtraction sialography: technique, advantages and results in 107 cases.

Sialographic examinations with the digital subtraction technique were performed in 107 salivary glands (90 parotid and 17 submandibular) of 99 patients. Diagnostic and technical advantages of the digital imaging and subtraction for sialography were investigated. Superior quality enabled detailed imaging of the entire ductal system. Reduced radiation exposure, short examination time and almost painless examinations with good patient tolerance proved to be the major advantages of digital subtraction sialography as a diagnostic tool.


Aberrations in X-ray output waveforms of radiological generators.

The waveform produced by variations in the output of radiological X-ray tubes during exposure was recorded by a solid state detector and oscilloscope in 14 different systems. Aberrations from the expected rectangular shape were observed in 11 of them, of which, 8 had faults due to bad service or improper installation. In some cases these faults affected the kVp rectification. This resulted in beam quality variations during the exposure which may have caused an increase in the patient dose. The ripple on the output waveform was also measured and proved to depend on the kVp.


Safety and tolerability of iodixanol in healthy volunteers with reference to two monomeric X-ray contrast media.

The low osmolar, non-ionic X-ray contrast media have shown a lower frequency of adverse events than the older ionic ones. In this study changes in routine clinical-chemical parameters in blood and urine, vital signs and adverse events were recorded in six groups of 10 healthy male volunteers receiving either iodixanol, a new non-ionic, dimeric X-ray contrast medium for general vascular use, or one of the two non-ionic, monomeric contrast media iopentol and iopamidol. Minor decreases were observed in the values for haemoglobin, haematocrit and erythrocytes 5 min and 3 days after injection of iodixanol. A minor increase was seen in platelets and total protein after 3 days. A transient increase in serum osmolality was seen 5 min after the injections of iopentol and iopamidol. This was not seen in any iodixanol group. The level of thyrotropin showed an increase in all groups at 3 days. It was back to normal within 21 days. No changes of clinical importance were seen regarding blood pressure, heart rate or ECG in any volunteer. No severe adverse events were reported. All events were of short duration, and of mild or moderate intensity. The results, however, may indicate a lower frequency of adverse events/discomfort after the administration of the dimeric iodixanol than the 2 monomeric contrast media iopentol and iopamidol.


Productivity of radiologists in the United States by imaging technique: a 16-year analysis based upon relative value units.

Professional Relative Value Units (RVUs) quantifying productivity of radiologists in the United States were used to study trends from 1973 to 1989 in the distribution of productivity among the various imaging techniques. Data from a 1989 survey were used to estimate the distribution of radiology examinations among techniques for 1989. A difficulty index (RVUs per examination) was calculated for each technique weighted by actual CPT-code occurrences reported in that survey. An RVU workload was estimated for each technique by multiplying the occurrences of the technique by its corresponding difficulty index. This analysis was applied first to the 1989 data, and second, retrospectively, to data from the literature that gave the distribution by technique of estimated national procedures for 1973 and 1980. The number of studies and RVUs in all techniques has increased from 1973 to 1989 with a relatively greater increase in the percentage of mammography and of sectional imaging examinations. Differences in difficulty index between the techniques leverage the changes in occurrence, causing a dramatic increase in the percentage of RVU workload represented by sectional imaging. The percentage of procedures and RVUs represented by vascular/interventional has remained relatively constant. The overall difficulty index has risen by 18% from 1973 to 1989. These trends should influence the allocation of space, equipment, and human resources in radiology department planning and management.


How to improve the quality of patient care and still save money in the radiology department.

1, A pediatric radiology department at an institution such as Minneapolis Children's Medical Center is a true microcosm of the gigantic radiology department of a general hospital. Our positive experiences with IMACS discussed above should be even more profound and profitable for the larger medical institutions. 2, IMACS did improve service and communications among radiologists, referring clinicians and the hospital staff. Both the old and new images needed for review and comparison are presently available for the clinicians on the nursing stations as soon as the current studies have been completed. 3, IMACS allowed us to reduce the number of films lost, misplaced or misfiled and reduced the interpretation delays by keeping all the films in the radiology department. This has resulted in improvement in the overall productivity of the radiology staff and the referring clinicians. 4, The cost of IMACS was paid for through additional revenue capture, increased productivity and a decrease in the expenses in the radiology department in less than one year. These benefits should continue for several more years without the need for any additional expenses. 5, Despite these initial successes, there are several issues which must be addressed before total computerization of the radiology services and a "filmless" radiology department can be created. A. The speed of an available workstation is totally inadequate for the day to day clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)


Policy development for CT and MRI services in Manitoba.

Economic forces are changing Canadian medicine. There are four hospitals in Manitoba with CT services and eight were planning to add services based on public subscription, internal transfer of resources and expected growth. The Ministry of Health requested an in depth report and review. Analysis of clinical activity for 287 disease categories from 13,996,240 physician claims and 149,480 hospital discharges reveal that 33,552 CT examinations are reasonable for 1.1 million people. The cost of operating each scanner is one million dollars per year. A formal review process of the report by the 12 hospitals and 7 selected experts was conducted. An advisory committee of all interested parties recommended that no further resources be allocated without proven clinical need and that a strong management committee be reactivated. MRI growth for nervous disease is expected to replace much CT activity in the next five years.


A survey on critical qualities and information sources on products purchased to the radiology department.

A survey on critical product qualities and sources of information on contrast media, CT and ultrasound machines, X-ray laboratories, angiography catheters and film was completed by 79% of the heads of radiology departments at Swedish hospitals. The respondents were asked to rank in order of preference as important information sources; own experience, opinions of colleagues, influence by sales representatives at the hospital or outside, fairs, congresses and scientific articles. The qualities of contrast media to rank were; low frequency of serious side-effects, low frequency of patient discomfort, easiness to handle, package size and price. For the other products technical performance, terms of delivery, terms of maintenance and price were ranked. Most important for contrast media was low frequency of serious side-effects and for the other products it was technical performance. The most important source of information regarding all products was the experience of the radiologist himself. In conclusion; high quality of the products and, safety and comfort of the patients are favoured over low price.


Screening mammography program delay recommended by Manitoba working group: issues for radiology.

Assignment: A working group, appointed by government, examined the advisability of implementing a mammography screening program and prepared a cost analysis. Present Manitoba activity (45,695) is a mixture of clinical mammography (10,000) and unorganized screening, mammographies (35,695) at an annual screening cost of $2.8 million. Canadian policy reports, program descriptions in other countries and critical reviews were analyzed. A steady-state clinical and financial model was constructed. A controlled screening program enrolling 80% of women 50-69 years will cost $2.6 million per year plus $0.65 million new clinical costs limited to 4 years. Recommendations; Six were made: delay implementation awaiting more evidence of benefit, discourage use in asymptomatic women under 50 years, develop information programs for women and health professionals, establish an advisory group and participate in research directed to a eventual decision.


A model for an outpatient imaging center.

U.S. federally imposed efforts to regulate joint venturing are a result of certain physician strategies to circumvent anti-kickback statutes by investing in clinics, labs, and facilities for self-referral. This article addresses the ethical debate on physician ownership, MRI as an evolving modality, the 1989 Ethics in Patient Referrals Act and the subsequently released "safe harbors," and finally, describes an existing model for physician/hospital ownership in an outpatient MRI facility.


William Beaumont Hospital Imaging Center design update.

The William Beaumont Imaging Center is designed to bridge the gap between conventional and totally digital imaging technology. Reverse capacity and flexibility are designed into the building and it's systems to facilitate the transition at minimal cost and disruption to daily operations.


Radiology department design to accommodate the future introduction of global PACS.

In the light of the continuing development of pictorial archiving and communication systems (PACS) and image management and communications (IMAC) systems it is appropriate to consider the provision that should be made in the design of a new or renovated department of radiology to accommodate these new technologies at either an earlier or later date. This paper considers three particular aspects of the influence of PACS on future department design: (1) the requirement for either more or less total department gross square feet, (2) the provision for the specific allocation of spaces at certain locations for PACS equipment and functions, and (3) the provision for dedicated pathways for fiber optic communications among the many locations in the department where PACS components would be located.