The pathobiology of bronchial asthma.

Early studies of patients dying from status asthmaticus revealed marked inflammation of the bronchial tree. Subsequent histological studies of the airways and examination of bronchoalveolar lavage fluid of subjects with mild asthma have confirmed the presence of airway inflammation in life. There is epithelial edema and desquamation, subepithelial deposition of collagen and fibronectin, and an inflammatory cell infiltrate in the mucosa. There are increased numbers of activated eosinophils, CD25-positive T lymphocytes, and immature macrophages with the phenotypic characteristics of blood monocytes. An increased expression of HLA class II is present on epithelium, macrophages, and other infiltrating cells. The severity of clinical asthma correlates with several measurements of the severity of the inflammatory response, suggesting a crucial role for airway inflammation in the pathophysiology of the disease. There is considerable interest and research into the mechanisms underlying the pathogenesis and maintenance of the inflammatory response in asthma. The development and maintenance of the inflammatory response in asthma is likely to be a consequence of a complicated interaction between various cells and the mediators they generate. The characterization of an ever-increasing number of cytokines is of particular interest. Interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor are hematopoietic growth factors that increase the survival of eosinophils in culture and enhance certain eosinophil functions, such as mediator generation and toxicity. Alveolar macrophages derived from asthmatic subjects produce twofold to threefold more GM-CSF than do those from normal control subjects. Using in situ hybridization, the presence of IL-5 mRNA has been demonstrated in bronchial biopsies from asthmatic subjects. Thus IL-3, IL-5, and GM-CSF influence eosinophil function and survival, and may be generated by T lymphocytes and/or alveolar macrophages within the airways in asthma. In addition to these three cytokines, IL-4 and interferon-gamma may be crucial to the regulation of IgE biosynthesis. TNF-alpha and IL-1 are potentially important in the up-regulation of endothelial adhesion molecules. An important step in the recruitment of leukocytes to an inflammatory focus is margination to the vascular endothelium. Our understanding of the molecular events involved in migration of leukocytes to an inflammatory focus has been advanced by the discovery and characterization of a variety of cell adhesion molecules. The potential role of ELAM-1 and ICAM-1 in allergic inflammation is suggested by their up-regulation on vascular endothelium in association with late cutaneous responses to allergen and by their role in certain primate models of asthma.(ABSTRACT TRUNCATED AT 400 WORDS)


[The local immune system of ocular surface].

Local immunity on the ocular surface was observed in guinea pigs immunized with horseradish peroxidase (HRP) by determining the activity of a specific antibody in local sites of the conjunctiva by the enzyme-antigen method, which enables a specific antibody to be stained. In addition, immunohistochemical study of the localization of IgA was performed by the enzyme-labelled antibody method. The enzyme-antigen method revealed a number of positive cells in the subconjunctival tissue and the parafollicular area of conjunctival-associated lymphoid tissue. These cells were identified as plasma cells by electron microscopy. The mirror section technique revealed that the cells positive for the enzyme-antigen method were consistent with anti-IgA-positive cells at many sites. Thus the distribution of plasma cells secreting IgA-specific antibody responsible for local immunity on the ocular surface was observed immunohistochemically. The results suggest that immunocytes in the conjunctival-associated lymphoid tissue differentiate and mature into specific antibody-producing plasma cells.


[A flow cytometric study of the effects of benzalkonium chloride on the cell cycle].

The effects of benzalkonium chloride (BAK) on the cell cycle of Chang's cultured human conjunctival cells were investigated by a flow cytometer (FCM). The cells were exposed to BAK solutions for 60 sec and after 12-48 hrs were fixed in 20% ethanol, treated by 0.25% RNase and stained by 0.005% propidium iodide. DNA histograms were analyzed by the FCM. As a result, although many cells were damaged by exposure to solutions of 0.0025% or 0.005% BAK, they began to grow again 48 hrs later. BAK decreased red fluorescence intensity in DNA histograms. The histogram shifted to the left 12 hrs after the cells were exposed to 0.0025% or 0.005% BAK solutions and recovered 48 hrs later. The DNA synthetic phase of the cell cycle was inhibited by exposure to solutions of 0.0025% BAK and then recovered 48 hrs later.


[Metabolic analysis of the diseased human corneal endothelium].

Redox states of the corneal endothelium in 42 recipient corneas obtained at the penetrating keratoplasty were measured non-invasively using ocular redox fluorometry. Autofluorescence from reduced pyridine nucleotides (PN) and oxidized flavoproteins (Fp) were measured, and the PN/Fp ratio was used as an indicator of the redox state. Endothelial damage was graded as normal, mildly damaged, moderately damaged, and severely damaged, based on the histopathological findings. Mildly damaged endothelium showed a significantly higher PN/Fp ratio than the that in normal endothelium whereas the ratio was significantly lower in the severely damaged endothelium. These changes in the redox state may represent compensation and decompensation processes of the endothelial metabolism. Ocular redox fluorometry was shown to be useful for the evaluation of the metabolic state in the human corneal endothelium.


[The immunosuppressive effects of 0.025% cyclosporin eye drops in alpha cyclodextrin on rabbit corneal allografts].

We reported the ocular penetration of cyclosporin (CYA) and the immunosuppressive effect of rabbit corneal allograft using 0.025% CYA eye drops in alpha-cyclodextrin (alpha-CD). Local application using 0.025% CYA in alpha-CD showed the concentration of 4,133 ng/gr in the cornea, but no detectable levels in aqueous humor and serum. All eyes (10/10) in the CYA eye drop group remained clear for 100 days after corneal allografting. CYA eye drops halted and suppressed the corneal allograft's immune reaction when the treatment was begun early in the initial phase of rejection. These results indicate that 0.025% CYA eye drops in alpha-CD penetrate the cornea 5 to 10 times more than CYA eye drops in lipophilic vehicles. Furthermore, they are extremely effective in suppressing the immune reaction of corneal grafts.


[Investigation of glutathione-S-transferase isozymes in human lenses].

Glutathione-S-Transferase (GST) isozymes in human lenses were investigated by the immunoenzymatic method using antibody against human liver GST2 and GST3 after polyacrylamide gel isoelectric focusing (western blotting method). Also, rocket immunoelectrophoresis was carried out for the detection of GST1. It was found that GST1 in lens also showed a polymorphism. The GST2 was not found in human clear lenses as well cataractous lenses. In addition, crossreacting materials against both antisera of GST2 and 3 were detected in the pH 6-7 area of the gel in all human lenses.


[Changes in rabbit lens epithelial cells after intravitreal silicone oil injection].

Using adult albino rabbits, the clinical course of lens opacity and morphological changes of lens epithelial cells were observed from 2 weeks to 3 months after intravitreal silicone oil injection. Simple vitrectomy was performed in both rabbit eyes. One eye with silicone oil injection served as an experimental eye, while another control eye did not receive any injection. Seven examined eyes showed early posterior subcapsular lens opacity from one month after silicone oil injection by slit-lamp microscopy. Small intracellular vacuoles near to the interdigitation of the lens epithelial cells were observed in the 7 eyes from 2 weeks after the procedure by transmission electron microscopy. These changes were not observed in 7 control eyes. As a result, it is surmised that cataract formation after intravitreal silicone oil injection may be associated with morphological changes of the lens epithelial cells.


[Dynamic changes in the organophosphate metabolites of the lenses affected by endotoxin and S-antigen induced uveitis].

Using 31P-NMR spectroscopy, the authors observed dynamic changes in the organophosphate metabolites in the lenses of two groups of Lewis rats affected by experimental uveitis induced by injecting Salmonella lipopolysaccharide (n = 20) or S-antigen (n = 25). A comparative study was done on the metabolic changes, the degree of inflammation, and histological changes in the rat lenses. Dynamic changes in the organophosphate profile in the lenses were measured by 31P-NMR spectroscopy. Only inorganic phosphate showed a significant increase (p less than 0.05) related to the increased inflammation in the endotoxin group, but the lenses showed no morphological change. Choline phosphate, adenosine triphosphate, and inorganic phosphate increased significantly (p less than 0.01) in the acute stage of inflammation, but a significant decrease (p less than 0.01) was evident from the peak of inflammation, following the histological destruction of the lenses. Our results indicated that in experimental uveitis dynamic changes in the organophosphate profile of the lenses were closely related to the protecting reaction against the stress caused by inflammation. Furthermore, we theorized that the generation of the secondary cataract was associated with the decreased metabolism of the phosphate compounds.


[Ciliary body changes associate with aldose reductase in galactosemic rats (2)].

Morphological changes of the ciliary body epithelium in rats fed a 50% galactose diet for 18 months with or without aldose reductase inhibitor (ARI: FR74366, Fujisawa) were investigated on coronal sections by both the light microscopic observation and the measurement of the area of non-pigmented epithelium (non-PE) as the ratio of non-PE/PE. The measurement was performed with color image analyzer. Structural change (hypertrophy) was observed only in non-pigmented epithelial cells of galactosemic rats. In contrast, no hypertrophic changes were seen in galactosemic rats treated with FR74366. These results strongly suggest that aldose reductase is associated with hypertrophic change of non-pigmented epithelial cells of the ciliary body as one of the diabetic complications.


[Possible mechanisms of inositol phosphate-diacylglycerol signalling pathway in the regulation of intraocular pressure].

To clarify the role of the inositol phosphate diacylglycerol (IP/DAG) signalling pathway in the regulation of intraocular pressure (IOP), the effect of tumor promoter phorbol ester (PMA) and Ca ionophore (A23187) on IOP responses was examined in albino rabbits. PMA stimulates protein kinase C (PKC) directly and A23187 elevates intracellular Ca2+ concentration. In this study, the topical application of 10 microM PMA or 15 microM A23187 slightly reduced IOP. However topical application of both 10 microM PMA and 15 microM A23187 significantly reduced IOP. The maximum IOP decrease was 5.0 mmHg. This decrease was inhibited by pretreatment with 0.5 microM staurosporin, a PKC inhibitor. Quantitative changes of inositol 1,4,5-trisphosphate (IP3) and PKC activity in cultured ciliary epithelia (CE), stimulated with several ocular hypotensive agents were also studied. When cultured CE was stimulated with 50 microM carbachol, the PKC activity and IP3 content rapidly increased. When CE was stimulated with 50 microM epinephrine, isoproterenol or timolol, PKC activity did not show any change and IP3 level declined. These studies suggest that the IP/DAG signalling pathway somehow mediates aqueous dynamic changes in ciliary epithelia.


[Measurement of blood velocity of rabbit iris by laser speckle flowgraphy].

We developed laser speckle flowgraphy which displays the relative velocity of blood microcirculation as a color map in two dimensions. We applied this method to the iris in 10 eyes of 5 normal white rabbits under general anesthesia. The coefficient of variation was small and averaged 5.6. There was no significant difference in the values measured on 3 consecutive days. The blood velocity in the iris increased significantly during experimental ocular hypotony and decreased during ocular hypertension and 2 hours after instillation of timolol (p less than 0.05). These findings indicate that the present method is of value in assessing the relative velocity of iris microcirculation in vivo and that topical instillation of timolol induces decrease of blood flow in the iris and, possibly, in the ciliary body.


[Effects of carteolol on electroretinograms in isolated perfused cat eye].

Effects of carteolol on ERG b-wave amplitude were investigated in dark adapted isolated perfused cat eyes. Carteolol enhanced ERG b-waves with both strong stimuli that reflect the function of both the rod and cone systems, and weak stimuli that reflect the function of the rod system. These observations suggest the following two ideas i.e.: 1. Carteolol increases the flow in retinal vessels of perfusate. or 2. Carteolol has interaction with retinal beta-adrenergic receptors related to the origin of the ERG b-wave. It is likely that both participate in the intrinsic sympathomimetic activity and the release activity of the endothelium derived relaxing factor of carteolol.


[Transient patterns of serotonergic innervation in the rat visual cortex--normal development and effects of enucleation].

Serotonergic innervation formed transient dense aggregation in all rat primary sensory areas during early postnatal development. In the normal rat visual cortex, there were three stages in the transient aggregation of serotonin immunoreactive fibers from postnatal day (PND) 2 to 15. Primary aggregates appeared in the subplate prior to the differentiation of layer IV, and moved upward to the lower layer of cortical plate to form secondary aggregates. Secondary aggregation gave rise to ascending fibers on the cortical surface which were roughly grouped in columns (tertiary aggregation). The serotonin fibers of the tertiary aggregates were arranged in a lattice-like pattern in layer I, and were significantly altered either in size of distribution area or column number after monocular or binocular enucleation. These data indicate that the lattice-like pattern of serotonin innervation in neonatal rats may be an evolutionary precursor of the "blobs" seen in the higher primates.


[Natural history of intermittent exotropia--statistical study of preoperative strabismic angle in different age groups].

To clarify the natural history of intermittent exotropia, the authors statistically analysed the size of deviations between the initial and the last visit of unoperated intermittent exotropes. In younger patients who were followed for over five years, the magnitudes were almost the same throughout the follow-up periods. A statistical analysis of preoperative strabismic angles in operated cases of different age groups was also done. From comparable studies of the preoperative size of exodeviations in three different age groups, the deviations in distance fixation in adults were apparently larger than in children. We think the size of the deviation in distance fixation tends to increase with aging, but the increase was not so great for the older adult group. However, the size of the deviation in near fixation tended to steadily increase throughout aging, showing statistical significance among all three groups, children, adults in their twenties and thirties, and adults over forty. In the over forty group, the convergence insufficiency type of deviation was present in the majority.


[Evaluation of preoperative prism adaptation in patients with acquired esotropia].

A prospective study was carried out of the evaluation preoperative prism adaptation in 77 patients with acquired esotropia. Sixty-three patients who showed a stable esodeviation with prisms of 10 prism diopter or less by alternate prism cover test and fusion response to the prisms were classified as prism responders and were randomly classified into two groups. Thirty-one patients of prism responders underwent surgery based on the prism adapted angle. Patients in the other 32 cases were assigned to undergo surgery for their initially measured angle. On the other hand, 14 patients who did not respond to prism adaptation underwent surgery for their preoperative measured angle of deviation. Success rates with deviations of 0 to 10 prism diopters measured 1 year after surgery by the alternative prism cover test at 5 m and with fusion on Bagolini's striated glasses test were highest (26 [84%] of 31 patients) in prism adaptation responders who underwent surgery for prism determined angle and lowest (3 [21%] of 14 patients) in the prism adaptation nonresponder who showed no fusion response to the prisms.


[Frequency response of ocular counter-rolling analyzed with passive sinusoidal head roll].

Using a computerized motor-driven chair that oscillates the subject's head in the frontal plane and a real-time video processing system for analyzing torsional eye movements, the frequency response of ocular counter-rolling to passive, sinusoidal head rolling was studied in darkness in 3 normal subjects. The gain of counter-rolling increased its mean value from 0.22 (0.17 Hz) to 0.52 (1.33 Hz) along with the frequency of head oscillation. Its phase error with respect to ideal compensation was slight (173-181 deg). Furthermore, the gain of counter-rolling was increased slightly from 0.31 (+/- 5 deg) to 0.39 (+/- 20 deg) along with the amplitude of head oscillation. Our experimental results agreed with the characteristics of the frequency responses for voluntary head shaking previously reported by Collewijn and colleagues, except that counter-rolling had a slightly lower gain.


[A case of peripheral corneal ulcer accompanied by progressive systemic sclerosis].

A 61-year-old woman with progressive systemic sclerosis developed bilateral peripheral corneal ulcer. The corneal lesions were resistant to daily systemic treatment with 15 mg steroid and 50 mg cyclophosphamide. Corneal perforation occurred in her right eye 11 months after the onset of Raynaud's phenomenon and 3 months after the scleritis. Lamellar keratoplasty accompanied with Brown's operation was performed on both eyes. Graft melt and cicatricial corneal opacity developed postoperatively. Removed conjunctival tissue was examined immunohistochemically. HLA-DR protein positive monocytes infiltrated subepithelial tissue, demonstrating that the inflammation of the lesions was in the active stage. Not only perforin but also suppressor/cytotoxic T cell positive reactions were observed, which revealed an involvement of the T cell immune system in the present case.


Ketamine, Telazol, xylazine and detomidine. A comparative anesthetic drug combinations study in ponies.

This study was designed to assess the effects of 5 anesthetic drug combinations in ponies: (1) ketamine 2.75 mg/kg, xylazine 1.0 mg/kg (KX), (2) Telazol 1.65 mg/kg, xylazine 1.0 mg/kg (TX), (3) Telazol 2 mg/kg, detomidine 20 micrograms/kg (TD-20), (4) Telazol 2 mg/kg, detomidine 40 micrograms/kg (TD-40), (5) Telazol 3 mg/kg, detomidine 60 micrograms/kg (TD-60). All drugs were given iv with xylazine or detomidine preceding ketamine or Telazol by 5 min. Heart rate was decreased significantly from 5 min to arousal after TD-20 but only at 60 and 90 min after TD-40 and TD-60 respectively. Respiratory rate was decreased significantly for all ponies. Induction time did not differ between treatments. Duration of analgesia was 10 min for KX, 22.2 min for TX, 27.5 min for TD-20, 32.5 min for TD-40, and 70 min for TD-60. Arousal time was significantly longer with detomidine and Telazol. Smoothness of recovery was judged best in ponies receiving KX and TD-40. All ponies stood unassisted 30 min after signs of arousal.


The role of endotoxins in induced ruminal acidosis in calves.

Experimentally induced ruminal acidosis was carried out in 4 calves to investigate the possibility of resorption of endotoxins from Gram negative bacteria originating from the gastro-intestinal tract. The ruminal acidosis was induced by overfeeding of oats and the effect was evaluated by clinical and blood biochemical changes. Blood samples were collected every 2 h for 60 h before and after experimental feeding. The animals showed signs of ruminal acidosis and also the clinical and blood biochemical changes were similar to those seen after experimental endotoxaemia. However, although being less dramatic the changes in many relevant parameters such as an increase in prostaglandin F metabolite levels, body temperature, endotoxins and a decrease in iron indicate that an endotoxaemic state had occurred. The results of the present study show that ruminal acidosis/stasis is linked to resorption of endotoxins from the gastro-intestinal tract causing endotoxaemia/endotoxicosis.


The role of endotoxins in methscopolamine induced ruminal stasis in calves.

Methscopolamine was used to induce ruminal stasis in calves. Clinical and blood biochemical parameters were studied to judge the possible role of gastro-intestinal endotoxins from Gram-negative bacteria. Two trials were carried out where one injection of 100 mg and 3 consecutive injections of 70 mg of methscopolamine were administered. The animals showed signs of ruminal stasis. General clinical signs and changes in blood biochemical parameters were similar to what is found in endotoxaemia or in induced ruminal acidosis. Relevant parameters such as prostaglandin F2 alpha metabolite, endotoxin, iron, zinc, calcium and glutamate dehydrogenase changed significantly indicating exposure of endotoxins.


Effect of hypophosphatemia on muscle metabolism after exercise in pigs.

Five Swedish Landrace pigs with a mean weight of 51 +/- 5 kg performed an exercise test on a treadmill at a speed of 1.8 m/s and a duration of 10 min. Hypophosphatemia was then induced in these pigs by addition of aluminium hydroxide (liquid antacid) to the normal feed. After 3 weeks, the exercise test was repeated when the mean weight of the pigs was 65 +/- 9 kg. Five other Swedish Landrace pigs with a mean weight of 72 +/- 4 kg performed a similar exercise test. Muscle biopsies from M. biceps and blood samples were taken from all pigs 3-5 days before and immediately after each exercise test. Hypophosphatemic pigs had significantly lower serum phosphate and higher aluminium levels than normophosphatemic pigs. In all pigs, glycogen content in muscle decreased significantly (-108 to -135 mmol/kg muscle) with exercise while no changes were seen in adenosine triphosphate, creatine phosphate or inorganic phosphate concentrations. In normophosphatemic pigs, glucose-6-phosphate and lactate concentrations increased significantly during exercise by 2-4 mmol/kg and 12.8-14.4 mmol/kg, respectively. However, in hypophosphatemic pigs, glucose-6-phosphate concentrations decreased significantly during exercise by 4.4 mmol/kg and lactate levels were unchanged. These results indicate that low serum inorganic phosphate levels influence muscle metabolism and glycolysis in connection with physical exercise.


Early foetal death in the mare. Histological, bacteriological and cytological findings in the endometrium.

Fifteen mares which had each lost their pregnancies 2 to 8 times during the preceding 6 years were used in a study comprising 1 or 2 breeding seasons for each mare. During the research period all 15 mares conceived and 10 of the mares had normal pregnancies in the 1st experimental year. Five mares resorbed/aborted once or twice during the 1st year. This was followed by a pregnancy that terminated in a live foal. Histopathological examinations of uterine biopsies showed a wide range of histopathological conditions, from absence of changes excessive for the mare's age and parity to the most severe changes of the endometrium. Most likely, endometritis, acute as well as chronic degenerative endometritis, is the most common cause of early foetal death in the mare. Good breeding management is essential and was often enough to make the mares produce a foal. Additional treatment was needed in some of the mares and was based on the course of the conceptus loss and the condition of the endometrium, as determined by clinical, histological, bacteriological and cytological examinations.


Occurrence of infectious fish diseases in fish farms in northern Finland.

A total of 47 fish located in 10 lake and river systems in northern Finland were examined for furunculosis, enteric redmouth diseases (ERM), viral fish diseases and the parasite Gyrodactylus salaris. Furunculosis was found in 2 fish farms in different watercourses, ERM in 8 fish farms in 3 watercourses and viral diseases were not found at all. G. salaris was looked for only in salmon and rainbow trout and was found in both species in 3 farms belonging to 2 watercourses.


Occurrence of different serotypes of Erysipelothrix rhusiopathiae in retail pork and fish.

Retail pork (38 samples), cod (10 samples) and herring (10 samples) were obtained from 12 stores in the area of Lund in southern Sweden during September and October 1990. Erysipelothrix rhusiopathiae was isolated from 50% of the pork samples, 60% of the cod samples and from 30% of the samples from herring. Serotype 2 dominated on retail pork as well as on fish samples constituting 53% of the pork isolates (10 strains) and 33% of the cod isolates (2 strains). All E. rhusiopathiae isolates originating from herring were serotype 2 (3 strains). Serotypes 1b, 6, and 8 were isolated from retail pork only (6, 2 and 1 strains, respectively). Serotype 5 was isolated from cod only (3 strains) and so was serotype 9 (1 strain). The public health hazards with the occurrence of virulent strains of Erysipelothrix rhusiopathiae in retail pork and fish are discussed.


Toxoplasmosis and border disease in 54 Swedish sheep flocks. Seroprevalence and incidence during one gestation period.

Serum samples from 704 animals from 54 Swedish sheep flocks were analysed by ELISA twice during 1 breeding season for antibodies to Toxoplasma gondii and border disease virus (BDV). An ELISA, originally developed for the detection of antibodies to bovine viral diarrhoea virus (BVDV) in cattle, was assessed on sheep sera and the results were compared with those obtained in a virus neutralization test. The correlation between the 2 assays proved good. Before breeding, 132 (19%) sheep in 42 flocks had antibodies to T. gondii and 7 (1%) sheep in 5 flocks were seropositive to BDV. During the observation period 4 sheep seroconverted to T. gondii and 13 to BDV, giving an incidence rate of 0.7% and 1.9% respectively. No clinical signs due to the infections were observed. In 5 flocks the frequency of barrenness, abortion or stillbirths exceeded 5%, 5% and 8%, respectively, but there was no evidence that this was attributable to the agents studied. The proportion of BDV-positive flocks was significantly higher among flocks that had been in contact with cattle than among those that had not.


MR measurement of blood flow in the cardiovascular system.

Methods for measurement of blood flow with MR were devised many years ago but have been used for diagnosis in only the past few years. The two methods of measurement that have been used most extensively are based on the principles of time of flight and phase shift. A number of factors can influence the accuracy of MR measurements of blood flow. In vitro studies using flow phantoms have verified the accuracy of the phase-shift technique for measuring flow velocities exceeding 5 m/sec, which for practical purposes, encompasses the peak flow encountered in cardiovascular disorders. The flow measurements have been used to quantify valvular heart disease, congenital heart disease, pulmonary arterial disease, thoracic aortic disease, and peripheral vascular disease.


Diagnosis of bronchiolitis obliterans in heart-lung transplantation patients: importance of bronchial dilatation on CT.

The purpose of this study was to evaluate the significance of bronchial dilatation identified on high-resolution CT scans obtained after heart-lung transplantation. Bronchial dilatation has been identified on pathologic specimens and on high-resolution CT scans of patients with severe bronchiolitis obliterans after lung transplantation, but this finding has not previously been systematically studied as a manifestation of this complication. We studied the high-resolution CT scans of 16 patients who had had heart and lung transplantation at least 1 year before, and compared the percentage of dilated bronchi with evidence of small airways disease shown on pulmonary function tests. We found a close correlation between the percentage of bronchi in the lower lobes that were dilated and the percent predicted forced expiratory volume in 1 sec, forced vital capacity, and forced expiratory flow between 25% and 75% of vital capacity. No other feature identified on high-resolution CT scans correlated with pulmonary function abnormalities. We conclude that dilatation of the lower lobe bronchi is a good indicator of bronchiolitis obliterans in this population, and that the percentage of dilated bronchi generally increases with increasing pulmonary dysfunction.


Hypersensitivity pneumonitis: sensitivity of high-resolution CT in a population-based study.

Hypersensitivity pneumonitis refers to a group of pulmonary disorders caused by inhalation of organic or inorganic particulates by sensitized persons. The diagnosis relies on a constellation of findings: exposure to an offending antigen, characteristic signs and symptoms, abnormal chest findings on physical examination, and abnormalities on pulmonary function tests and radiographic evaluation. In population-based studies, the sensitivity of chest radiography for detection of this disease is relatively low. The aim of this study was to determine the sensitivity of high-resolution CT (HRCT) for detection of hypersensitivity pneumonitis diagnosed in a population of swimming-pool employees. Thirty-one symptomatic employees of a recreation center who were referred because of possible hypersensitivity pneumonitis were examined by using chest radiography, HRCT, and fiberoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Hypersensitivity pneumonitis was diagnosed in subjects who had two or more work-related signs or symptoms, abnormal results on transbronchial biopsies, and abnormal lymphocytosis as shown by examination of bronchoalveolar lavage fluid. The chest radiographs and HRCT scans were interpreted by consensus by two observers who were unaware of the clinical diagnosis. Only one of 11 subjects with a diagnosis of hypersensitivity pneumonitis had abnormal findings on a chest radiograph. Five had abnormal HRCT findings. The abnormality in each case consisted of small, poorly defined centrilobular nodules with variable profusion. No subject without the disease had abnormal HRCT findings. Those who had granulomas shown by lung biopsy were more likely to have abnormal HRCT findings than were those who had more subtle histologic abnormalities. The sensitivity of HRCT for the detection of hypersensitivity pneumonitis in a population-based study is greater than that of chest radiography. The finding of poorly defined centrilobular nodules on HRCT scans should prompt consideration of this disease.


Pulmonary sarcoidosis: changes on follow-up CT examination.

To determine serial changes in the pattern, distribution, and extent of disease over time, and to determine if any specific findings could be used to predict prognosis in patients with pulmonary sarcoidosis, we reviewed the CT scans of 18 patients with pulmonary sarcoidosis. The study included 18 patients with biopsy-proved sarcoidosis and pulmonary abnormalities who had two serial high-resolution CT examinations (1.5-mm collimation, high-spatial-frequency reconstruction algorithm) 4-49 months apart. Initial and follow-up CT scans were evaluated independently and then directly compared with each other by two observers. Scans were assessed for the presence, extent, and severity of ground-glass, nodular, and irregular linear opacities; interlobular septal thickening; cystic air spaces; and architectural distortion. If a finding was predominant, it was noted. Reversible findings included ground-glass, nodular, and irregular linear opacities and septal thickening. Irreversible findings included cystic air spaces and architectural distortion. Follow-up CT showed overall improvement in 12 of 18 patients, progression in five, and no change in one. A predominant pattern of disease could be determined for each patient. Fourteen patients had predominant nodular opacities; of these, 11 had improved by follow-up. Four had predominant irregular linear opacities; of these, three showed progression of disease on follow-up. The presence of any other specific abnormalities, including ground-glass opacities, was not helpful in predicting improvement or worsening of disease on the follow-up examination. In pulmonary sarcoidosis, ground-glass, nodular, and irregular linear opacities and interlobular septal thickening represent potentially reversible disease, while cystic air spaces and architectural distortion are irreversible findings. Follow-up CT usually shows improvement in patients with predominant nodular opacities, while disease tends to progress in patients with predominant irregular opacities.


Solitary breast papilloma: comparison of mammographic, galactographic, and pathologic findings.

Our purpose was to determine the mammographic/galactographic features of solitary breast papillomas and to correlate these features with the pathologic findings. Retrospective review of pathology files revealed 72 women in whom breast biopsy reports described a solitary papilloma. All patients with additional pathologic abnormalities were excluded from this study. Patients meeting the pathologic criteria and for whom mammograms, galactograms, or both were available and had been obtained within 6 months before biopsy were included. Twenty-four women met these criteria and form the basis of this study. Presenting clinical signs and symptoms were reviewed. Abnormal mammographic/galactographic findings were correlated with pathologic features. Nipple discharge was present in 21 (88%) of 24 patients, two (8%) of 24 patients had abnormal findings on screening mammography, and one patient had a palpable mass that was visible on mammograms. Eight (42%) of 19 mammograms had abnormal findings, including dilated duct(s) in five cases (26%), nodules in two cases (11%), and microcalcifications in one case (5%). All technically adequate galactograms (13/15) had abnormal findings, with 12 (92%) of 13 showing an intraluminal filling defect. The other technically adequate galactogram (8%) showed only a solitary obstructed duct. Ductal dilatation was greatest at or central to the papilloma on 12 (92%) of 13 galactograms. Imaging features correlated well with the histologic findings. Patients with solitary papillomas most commonly have nipple discharge, normal mammographic findings, and a galactographic filling defect. Galactography is useful for localizing papillomas.


Mammography in women with axillary lymphadenopathy and normal breasts on physical examination: value in detecting occult breast carcinoma.

The purpose of this study was to determine the value of mammography in detecting occult carcinoma in patients with axillary adenopathy and normal breasts on physical examination. We analyzed the results of mammography performed in 17 patients; all women had palpable axillary lymphadenopathy of unknown origin and all had normal breasts on physical examination. In 10 of the 17 patients, mammographic findings were abnormal. The mammographic finding of axillary adenopathy in seven patients was inconsequential because the nodes were evident on physical examination. Three patients had abnormal mammographic findings that were potentially significant, including one with a poorly defined mass suggestive of breast carcinoma, one with a subcutaneous nodule, and one with parenchymal breast edema. Two of 17 patients had an occult breast cancer. In only one of the patients was the cancer detected on mammography. The other patient had undergone prior left mastectomy and was thought to have metastases to the right axilla from the contralateral breast. Mammographic findings in this latter patient were normal. While occult breast carcinoma was relatively common in our series (two of 17 patients), the ability to detect the tumor with mammography was disappointing (one of two patients). This may be explained by the fact that one postmastectomy patient with occult carcinoma had metastatic disease to the contralateral axilla and a normal remaining breast, which was pathologically confirmed at mastectomy. Our experience suggests that mammography is valuable in patients with normal breasts on physical examination who have primary carcinoma involving ipsilateral axillary lymph nodes. The procedure should be included in the diagnostic evaluation of patients with axillary adenopathy in order to detect the unusual case of occult breast carcinoma.


Left-lobe hepatic transplants: spectrum of normal imaging findings.

The limited availability of suitable size-matched donor whole organs has been a major cause of morbidity and mortality in infants and children requiring liver transplantation. Techniques for transplanting segments of the liver have successfully addressed this problem. The surgical anatomy of the left hepatic lobe transplant is unique in three primary respects: the cut edge, the presence of an enteric Roux loop for biliary drainage, and the alteration in the position and number of hepatic vessels. The spectrum of normal imaging findings in 17 left-lobe allografts is illustrated.


Chronic biliary-type pain in the absence of gallstones: the value of cholecystokinin cholescintigraphy.

Radiologic criteria for the diagnosis of gallbladder disease largely rest on the detection of calculi. Surgeons are reluctant to do a cholecystectomy in patients with symptoms of gallbladder disease if the results of sonography or cholecystography are normal. Consequently these patients are often left with no satisfactory treatment. Such patients may have chronic acalculous cholecystitis, partial obstruction of the cystic duct, or gallbladder dyskinesia. Increasing evidence indicates that at least some of these patients have decreased gallbladder emptying in response to a stimulus such as a test meal or cholecystokinin. Impaired emptying shown by cholecystokinin cholescintigraphy may be useful for predicting which patients with typical biliary-type pain but no evidence of calculi will be cured by cholecystectomy.


Membranous obstruction of the inferior vena cava: comparison of findings at sonography, CT, and venography.

Membranous or segmental obstruction of the inferior vena cava is one of the common causes of chronic Budd-Chiari syndrome. In this study, the venographic findings are compared with the results of sonography and CT in order to ascertain their role in the management of these cases. Fifteen patients with membranous (n = 8) or segmental (n = 7) obstruction of the inferior vena cava who had been examined with sonography and CT were studied retrospectively. Diagnosis was made at surgery (n = 3) or by venacavography (n = 12). Sonographic findings were analyzed on the basis of the initial report, and CT findings were reviewed retrospectively with knowledge of the sonographic findings. Sonography showed membranous obstruction (n = 5), segmental cordlike obstruction (n = 3), and unspecified obstruction (n = 5) of the inferior vena cava, while CT showed a flap of the membrane (n = 1) and segmental narrowing or obstruction of the inferior vena cava (n = 7). In the remaining cases, the inferior vena cava either appeared normal (n = 6) or was not visualized (n = 1) on CT or was not described in the sonographic report (n = 2). In nine cases, CT showed one or several tiny calcific foci in the inferior vena cava. Sonography showed obliteration of at least one hepatic vein (n = 8) and of intrahepatic collateral vessels (n = 12), whereas CT was less sensitive in evaluating obliteration of intrahepatic veins (n = 4) and collateral vessels (n = 7). Sonography and CT both showed hepatic masses (n = 6), evidence of liver cirrhosis and portal hypertension (n = 14), hepatomegaly (n = 14), enlargement of the caudate lobe (n = 9), and intraabdominal (n = 11) and abdominal wall (n = 15) collateral vessels. Sonography was superior to CT in delineating pathologic venous anatomy of the inferior vena cava and hepatic veins whereas CT was better in evaluating hepatic cirrhosis and tumor. We believe that these techniques are useful complements to venography in the diagnosis and management of these cases.


Acute lower gastrointestinal hemorrhage: treatment by superselective embolization with polyvinyl alcohol particles.

The major risk of transcatheter embolotherapy for acute hemorrhage in the lower gastrointestinal tract is irreversible intestinal ischemia. The authors studied the efficacy and safety of superselective transcatheter embolization with polyvinyl alcohol particles in arresting acute hemorrhage in the lower gastrointestinal tract. All patients with clinical or scintigraphic evidence of acute hemorrhage in the lower gastrointestinal tract were considered for superselective embolization. The nine patients with angiograms that showed active hemorrhage in the lower gastrointestinal tract underwent the procedure. Superselective embolization was done through a 3-French catheter and was accomplished by using 100- to 590-microns polyvinyl alcohol particles. The segments of the intestinal tracts involved in the embolizations were examined for the presence of ischemia by endoscopy (n = 7) or histologic evaluation of a surgical specimen (n = 2) 2-44 days (mean, 11 days) after embolization or by clinical evaluation (n = 1). The lesions treated by this method were located in the colon (n = 8) and jejunum (n = 1). Immediate hemostasis was achieved in every case. Three patients had recurrent lower gastrointestinal hemorrhage 1-24 days (mean, 9 days) after initial embolization. Two of these patients had surgery, while one had a successful second embolization. Two asymptomatic patients were found endoscopically to have small areas of ischemia involving only the mucosa. Only one patient was shown to have severe mucosal ischemia; this involved the colon in a distribution that suggested it was not caused by the embolization. Ten superselective embolization procedures that used polyvinyl alcohol particles successfully controlled hemorrhage in the lower gastrointestinal tract in nine patients. In no case was intestinal infarction induced by the procedure, and only two endoscopically proved cases of asymptomatic mucosal ischemia occurred.


The density, contour, and thickness of the pancreas in diabetics: CT findings in 57 patients.

Insulin has a trophic effect on pancreatic acinar tissue, so the pancreas might be expected to atrophy in persons who have diabetes. Accordingly, we analyzed the density, contour (smooth or lobulated), and thickness of the pancreas on CT scans of diabetic patients and compared the results with those in control subjects. The prevalence of pancreatic lobulation (incisurae deeper than 2 mm) and its correlation with age in diabetic and control subjects were determined. The thickness of the pancreas was measured at three levels (head, body, tail). Three groups of diabetic patients were examined: 20 insulin-dependent patients, 25 patients not treated with nor dependent on insulin, and 12 patients treated with but not dependent on insulin. A control group included 57 nondiabetic patients. The ages of the control subjects were similar to those of the diabetic patients. The statistical significance of the differences between groups of diabetic patients and control subjects was estimated by using Student's t test for the values of density and thickness and the chi 2-test for the prevalence of pancreatic lobulation. The density of the pancreas in diabetic patients and control subjects was not statistically different. Diabetic patients had increased lobulation of the pancreas. All parts of the pancreas tended to be smaller in diabetic patients, but the degree of reduction varied. It was modest in the patients not treated with insulin, pronounced in insulin-dependent patients, and intermediate in non-insulin-dependent, insulin-treated patients. Moreover, the size of the body was significantly reduced in all three groups, whereas the size of the pancreatic head was preserved in patients not treated with insulin. In conclusion, CT of the pancreas shows that although density in diabetic patients is normal, lobulation is increased. Reduction in size involves the body of the pancreas more than other parts of the gland and is more pronounced in insulin-treated diabetic patients. CT of the pancreas might be useful to predict which diabetic patients will require insulin therapy.


Pancreatic disease: findings on state-of-the-art MR images.

Recent technical innovations have made MR imaging a useful technique for imaging the pancreas. The potential impact of MR imaging on the management and outcome of cases can be determined only by controlled prospective comparative studies; however, these cannot be performed adequately until the normal and abnormal appearances of the pancreas on state-of-the-art MR images are understood. This pictorial essay is presented to further this intermediate goal.


Diagnosis of acute appendicitis in pregnant women: value of sonography.

The diagnosis of acute appendicitis in pregnant women often is difficult to make on the basis of clinical findings, and radiologic examination is limited because of the potentially hazardous effects of radiation. This study was done to assess the value of sonography in the diagnosis of acute appendicitis in pregnant women. We obtained sonograms in 45 pregnant women with clinically suspected acute appendicitis. Our sonographic technique included graded-compression scanning. The left lateral decubitus position was used in the third trimester of gestation. The sonographic criterion for the diagnosis of acute appendicitis was visualization of an incompressible appendix with a maximal diameter greater than 7 mm. We correlated the sonographic findings with the surgical findings in 22 cases and with the results of clinical follow-up in 23 cases. Sonography could not be used to make the diagnosis in three (7%) of 45 patients because the size of the gravid uterus prevented use of the graded-compression technique. These three patients were in the third trimester of pregnancy (greater than 35 weeks' gestation). Sonographic findings were used as a basis for diagnosis in 42 cases. Acute appendicitis was diagnosed on the basis of sonograms in 16 patients, and in all but one of these patients, acute appendicitis was confirmed by surgical and pathologic findings. In the 42 cases in which the imaging findings indicated the diagnosis, the overall sensitivity of sonography was 100%, the specificity was 96%, and the accuracy was 98%. Our experience suggests that graded-compression sonography is a valuable procedure for detecting acute appendicitis in pregnant women despite technical difficulty in performing it during the third trimester of pregnancy.


Renal diseases in patients with AIDS: sonographic findings.

This essay illustrates the spectrum of sonographic findings of various renal manifestations of AIDS. The most common renal abnormality in patients with AIDS is nephropathy, which is manifested by deterioration of renal function and proteinuria. Acute tubular necrosis, intrarenal infections, focal nephrocalcinosis, hydronephrosis, and neoplasms also may occur.


Submucosal uterine leiomyomas: diagnosis of prolapse into the cervix and vagina based on MR imaging.

We describe the MR appearance, signs and symptoms, and pathologic findings in five patients with submucosal leiomyomas that prolapsed into the cervical or vaginal canal. During the past 3 years, five women aged 33-53 years (mean, 43 years) were identified prospectively at MR imaging as having prolapsing uterine leiomyomas. The diagnosis was confirmed by surgical pathology. MR imaging was performed on a 1.5-T unit, using both T1- and T2-weighted spin-echo or fast spin-echo sequences. The images were analyzed for signal intensity, presence of a stalk, and caudal extent of the prolapsed leiomyoma. These leiomyomas, the presence of prolapse, and the caudal extent of prolapse were detected prospectively on MR images in all five cases. Prospective localization of the stalk in two cases aided subsequent hysteroscopic resection. MR imaging correctly indicated the presence of hemorrhage in one, degeneration in a second, and the absence of these complications in two others. In the fifth case, a hemorrhagic focus in the distal tip of the leiomyoma was not detected on MR images obtained 3 days before surgery. MR imaging is useful for the diagnosis and characterization of uterine leiomyomas that have prolapsed into the cervical or vaginal canal.


Temporomandibular joint: relationship between MR evidence of effusion and the presence of pain and disk displacement.

The purpose of this study was to correlate MR evidence of joint effusion in the temporomandibular joint with symptoms of joint pain and the presence of disk displacement and arthrosis. The temporomandibular joints of 379 patients with clinical symptoms of temporomandibular joint disorders and 11 asymptomatic volunteers were imaged bilaterally. Sagittal and coronal proton density-weighted and T2-weighted images were obtained. Imaging findings of joint effusion were correlated with the presence of disk displacement and arthrosis and the symptom of pain. MR showed effusion in 7% of the joints with normal superior disk position, 40% of the joints with disk displacement with reduction, 50% of the joints with disk displacement without reduction, and 27% of the joints with arthrosis. Two of the control subjects had disk displacement with reduction; MR did not show joint effusion in any of the control subjects. A strong association was seen between joint effusion and joint pain. Joint effusion was seen in 46% of the joints on the more painful side and in 13% of the joints on the less painful side. The results show that temporomandibular joint effusions primarily occur in joints with disk displacement and are strongly associated with joint pain.


Injuries of the superior portion of the glenoid labrum involving the insertion of the biceps tendon: MR imaging findings in nine cases.

The goal of this investigation was to describe the MR appearance of traumatic fraying or detachment of the superior portion of the glenoid labrum including the insertion of the tendon of the long head of the biceps. This condition is caused either by an acute injury or by repeated overhead motion during participation in sports. In nine patients with such a lesion, the arthroscopic report and MR images were available for review. These patients were 22-64 years old (mean, 38). In four patients only fraying was noted during arthroscopy, in four patients the superior part of the labrum was detached together with the insertion of the biceps tendon, and in one case there was a bucket-handle tear of the superior portion of the labrum. The MR images were retrospectively evaluated by three osteoradiologists in conference. Signal changes within the labrum and detachment of the labrum were noted, and the findings were compared with the results of arthroscopy. MR imaging did not allow recognition of simple fraying. In two of the five cases with arthroscopic findings of detachment of the superior labrum from the glenoid rim, differentiation between complete and partial labral detachments was not possible even with MR arthrography. However, in these cases the patient's age and history led to the correct diagnosis. We conclude that early traumatic abnormalities of the superior portion of the labrum cannot be detected with MR imaging. Complete detachment, however, can be demonstrated if the patient's age and history are taken into consideration.


Value of unenhanced spin-echo MR imaging in distinguishing between synovitis and effusion of the knee.

We performed a study to determine if unenhanced spin-echo MR imaging can be used to differentiate effusion from synovitis of the knee joint. Unenhanced spin-echo MR imaging examinations of 1051 consecutive patients referred for evaluation of internal derangement of the knees were reviewed. Twelve of 550 knees with significant joint effusion also had thickened or irregular synovium. Of these, the cause of synovitis was proved in 10 patients. In the other two, the cause was unknown. Thickened synovium was of intermediate signal intensity on T1-weighted MR images compared with the lower signal intensity of joint effusion. In eight cases, the thickened synovium had an intermediate signal intensity on T2-weighted images relative to the high signal of the joint effusion. MR images in the other four cases showed increased signal intensity indistinguishable from that of joint effusion. Our experience suggests that unenhanced spin-echo MR images can be used to distinguish synovitis from effusion in the knee joint.


Elastofibroma: MR and CT appearance with radiologic-pathologic correlation.

The purpose of our study was to determine the MR and CT appearances of elastofibroma and correlate the imaging features with the underlying pathologic findings. We reviewed retrospectively the MR and CT findings in five cases of elastofibroma. All patients had a soft-tissue mass; one patient also complained of pain. The mean age of the patients was 71 years (range, 63-79 years). Four lesions occurred in the subscapular region, and one occurred in the thigh. In addition, we reviewed and compared the demographic data of 72 histologically proved cases for which we had archival data. Three of four lesions evaluated with spin-echo MR imaging were approximately isointense with skeletal muscle and contained areas with a signal intensity similar to that of fat; these corresponded to areas of dense collagen and interspersed fat, respectively. In the fourth case, the MR appearance was nonspecific. In one case, MR imaging with gadopentetate dimeglumine showed areas with and without enhancement. Three of four lesions evaluated with CT had variable margins, with tissue attenuation similar to that of the adjacent soft tissue as well as scattered areas of decreased attenuation, suggesting fat within the lesion. In one case, the lesion was well defined and relatively homogeneous with an attenuation less than that of skeletal muscle. The MR and CT features of elastofibroma are different from those of most other soft-tissue tumors, reflecting entrapped fat within a predominantly fibrous mass. Although these features are not pathognomonic, their presence in a subscapular lesion in an older patient suggests a presumptive diagnosis of elastofibroma.


Neoplastic diseases affecting the central skull base: CT and MR imaging.

Modern imaging techniques play a vital role in the diagnostic evaluation and follow-up of patients with neoplastic disease affecting the skull base. Many of these lesions have a high rate of recurrence if surgical removal is not complete. Newer, more aggressive surgical approaches can have a maximal effect only if the full extent of a lesion is known preoperatively. CT and MR imaging provide the surgeon with detailed information about every site of tumor involvement. Although these lesions are not common in clinical radiologic practice, the radiologist must be prepared to offer a reasonable differential diagnosis and a full evaluation of the extent of disease. This review presents some of the more commonly encountered tumors that can affect the skull base and describes their radiologic features, with emphasis on CT and MR imaging.


Diffusion MR imaging: clinical applications.

Water self-diffusion, a recently discovered source of contrast on MR images, has already shown promise for some clinical applications. Most studies have been of the brain, essentially for technical reasons. Diffusion is useful in distinguishing the different components of brain tumors (cystic regions, edema, necrosis) from the tumor core itself. Recent studies have shown that diffusion is anisotropic in brain white matter (i.e., dependent on the fiber tract's orientation in space), offering new insights into myelin disorders. Diffusion is also dramatically altered in the minutes following ischemic injury in the cat brain, which may have tremendous impact for the diagnosis and management of hyperacute stroke. With ultrafast acquisition schemes, diffusion imaging has also been used outside the CNS, for instance, in the eye and kidney. Future applications include diffusion-localized spectroscopy and temperature imaging. This article reviews recent progress in this field and suggests potential applications.


CT and MR imaging findings in adults with cerebellar medulloblastoma: comparison with findings in children.

The goal of this study was to determine if certain imaging features suggest the diagnosis of cerebellar medulloblastoma in adults and to determine how often the classic CT appearance seen in children is present in adults. The study included 28 adult patients with proved cerebellar medulloblastoma. The tumor was located in the cerebellar vermis in 14 patients and in a cerebellar hemisphere in 14 patients. Thirteen patients had unenhanced CT of the brain, all patients had contrast-enhanced CT, and eight patients had unenhanced MR imaging. The imaging features in adults were compared with those in children, as described in the literature. In our adult patients, all tumors were hyperdense compared with gray matter on unenhanced CT and showed a slight to moderate increase in density after injection of contrast medium. Thirteen lesions had well-defined margins, and 15 had poorly defined margins. Low-density areas consistent with cystic and necrotic degeneration were detected in 23 (82%) of the 28 tumors. By comparison, in children, medulloblastoma usually originates in the vermis. As in adults, the mass is hyperdense on unenhanced CT, but enhances markedly and homogeneously after injection of contrast medium. Usually no evidence of cyst formation or necrosis is seen, and the tumor margins are well defined. This classic CT appearance of medulloblastoma in children was identified in only three (11%) of the 28 adult patients. Medulloblastoma has a variable MR appearance in both children and adults. On T2-weighted images, lesions are hypo-, iso-, or hyperintense compared with normal gray matter. The CT findings of medulloblastoma in adults usually differ from those of medulloblastoma in children. The tumor has a variable and nonspecific appearance in adults and should always be considered in the differential diagnosis of a mass in the posterior fossa.


Diagnosis of liver disease in children: value of MR angiography.

We retrospectively studied the clinical use of MR angiography, a gradient-echo technique susceptible to motion, in the preoperative evaluation of the hepatic vasculature in children with liver disease. Twenty imaging examinations were performed in 18 patients 3 months to 10 years old (mean, 2.3 years). Eleven patients had liver tumors and seven had cirrhosis associated with biliary atresia, cystic fibrosis, and short-bowel syndrome. Respiratory motion artifacts were present in most patients, but all MR angiographic studies were technically adequate. Comparing MR angiograms with spin-echo images, we found that vascular visualization was better with MR angiography in 12 cases (60%), equal in five (25%), and worse in three (15%). In 10 of 20 cases, MR angiography provided additional vascular information not present on spin-echo images. MR angiography is a useful adjunct to spin-echo imaging for assessing hepatic vascular anatomy in children with liver disease.


Strategies for improving power in diagnostic radiology research.

Research studies in diagnostic radiology often compare the diagnostic abilities of two imaging techniques. The "power" of such studies is the probability that they will detect a difference in abilities of a certain amount when, indeed, such a difference does exist. This article outlines several strategies that can be used to assess and improve the power of radiologic diagnostic studies. These strategies include selection of cases and controls, matching, use of one-tailed tests, selection of significance level, and choice of sample size.


Relationships between upper-arm anthropometry and soft-tissue composition in postmenopausal women.

The value of upper-arm anthropometry as a measure of lean- and fat-tissue masses in 140 normal postmenopausal white women was assessed by studying the relationships of these measures to total and regional fat, and lean masses measured by dual-energy x-ray absorptiometry. Midarm circumference (MAC) was highly correlated with total and regional fat masses (r = 0.85-0.89, P less than 0.0001) but less so with lean-tissue masses (r = 0.26-0.34). Triceps-skinfold thickness was also correlated with fat masses (r = 0.70-0.74, P less than 0.0001) but not with lean mass (r = 0.02-0.09). The derived index, arm muscle area (AMA), was less closely correlated with fat mass than was MAC (r = 0.59-0.61), but its correlation with lean-tissue mass was comparable to that for MAC (r = 0.37-0.43). Multiple-regression analysis confirmed that the anthropometric indices were more closely correlated with fat than with lean mass. It is concluded that all these indices are useful measures of fat mass but that none, including AMA, is a specific index of lean-tissue mass in normal postmenopausal women.


Reduced tissue arachidonic acid concentration with chronic ethanol feeding in miniature pigs.

The effect of ethanol feeding on the essential fatty acid content of tissues has been contradictory. To define the effect, we analyzed fatty acid profiles in various tissues from five miniature pigs fed daily 105 kJ basal diet/kg body wt and 146 kJ ethanol/kg body wt, and also five control pigs pair-fed the same amount of basal diet but with corn starch substituted for ethanol. After 12 mo, biopsy samples were taken, and tissue fatty acid profiles were analyzed. In the phospholipid fraction from the ethanol group there was a uniform decrease in arachidonic acid (AA) and an increase in oleic acid in liver, serum, and muscle. AA was consistently decreased in the triglyceride fractions of liver, serum and subcutaneous adipose of the ethanol group. Possible explanations for this general reduction in tissue AA with ethanol feeding include decreased activities of delta 6 and delta 5 desaturases, and a displacement of AA from lipid fractions by other fatty acids.


Relationships between 3-y longitudinal changes in body mass index, waist-to-hip ratio, and metabolic variables in an active French female population.

Three-year longitudinal changes in body mass index (BMI), waist-to-hip ratio (WHR), and metabolic variables were examined in 209 active French women. For the entire group, a weak but significant positive association was found between change in BMI and change in WHR. However, analysis of covariance according to the degree of abdominal fat distribution showed a heterogeneity of this association that was confined to women with abdominal fat distribution. Changes in BMI were positively associated with changes in total cholesterol (P less than 0.05), triglycerides (P less than 0.10), and blood pressure (P less than 0.001), whereas changes in WHR were associated with changes in triglycerides (P less than 0.05) and diastolic blood pressure (P less than 0.10). These longitudinal results suggest that a more favorable body-fat pattern and metabolic profile might be achieved by reducing weight, or at least by preventing weight gain, particularly in women with high abdominal-fat distribution.


Massive overfeeding and energy balance in men: the Guru Walla model.

To determine the magnitude of the thermogenic response to a massive long-term overfeeding, an energy-balance study was carried out in nine lean, young Cameroonian men participating in a traditional fattening session: the Guru Walla. Food intake, body weight, body composition, activity, and metabolic rates were recorded during a 10-d baseline period and over the 61-65 d of fattening. Total energy expenditure (TEE) was measured by using doubly labeled water during the baseline period and the final 10 d of Guru Walla. Cumulative overfeeding consisted of 955 +/- 252 MJ (chi +/- SD) mainly as carbohydrate. Body-weight increase was 17 +/- 4 kg, 64-75% as fat. Metabolic rates increased but TEE did not. However, when accounting for the reduction in physical activity, substantial thermogenesis was observed but its amplitude was not greater than that observed under less extreme carbohydrate-overfeeding conditions. If luxuskonsumption does exist, it is not related to the magnitude of the cumulative overfeeding.


Effect of a zinc-fortified formula on immunocompetence and growth of malnourished infants.

This study attempted to define the possible contribution of zinc nutrition to immunocompetence and growth in severely malnourished infants. The effect of zinc supplementation was evaluated in marasmic infants during nutritional rehabilitation by using a controlled double-blind design in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same non-supplemented formula. Evaluation of immunocompetence, growth, and zinc, copper, and iron status was performed on admission and at 30, 60, and 105 d of nutritional rehabilitation. Although energy intake was similar in both groups, the zinc-supplemented infants had significantly higher linear growth gain, and their immune function improved as demonstrated by conversion of their delayed hypersensitivity skin reactions, enhanced lymphoproliferative response to PHA, and increased salivary IgA concentrations. Thus, the use of a zinc-fortified formula during nutritional rehabilitation can prevent the development of zinc deficiency and improve growth and immune function.


Protein-energy requirements of boys 12-14 y old determined by using the nitrogen-balance response to a mixed-protein diet.

Short-term nitrogen-balance response to graded intakes of a vegetable mixed-protein diet and to a milk-egg protein diet was tested in eight healthy male children aged 12-14 y. They received 72, 104, 136, and 168 mg N.kg body wt-1.d-1 for 10 d while on the mixed diet, and 160 mg N.kg-1.d-1 on the milk-egg diet. The mean regression equation was nitrogen balance = 0.64 (nitrogen intake)-74, all values are in mg N.kg-1.d-1. Apparent digestibility was 86% and 85% for the mixed and milk-egg diets when the subjects received 168 and 160 mg N.kg-1.d-1, respectively. Mean nitrogen intake for satisfactory nitrogen retention for growth on the mixed diet was 147 mg N.kg-1.d-1; the recommended protein allowance to cover 97.5% of the population, which was derived by using a CV of 12.5%, is 1.15 g protein.kg-1.d-1. We conclude that FAO/WHO/UNU recommendations are adequate, at least for short-term nitrogen retention; long-term studies are needed to evaluate the chronic safety of this protein allowance.


Morbidity and the growth of stunted and nonstunted children, and the effect of supplementation.

Children aged 9-24 mo were recruited by a survey of poor areas of Kingston, Jamaica. Stunted children were randomly assigned to supplementation or not. Weekly morbidity histories were taken for 2 y. Separate multiple regressions on each symptom for weight or length gain in 2-mo intervals showed significant reductions in weight gain with coughing, apathy, anorexia, diarrhea, and fever, ranging from -2.1 to -16.8 g/d ill. Apathy and diarrhea reduced gains in length (-0.26 and -0.20 mm/d ill). Significant reductions in linear growth with lower respiratory-tract infections (-0.16 mm/d ill) occurred only in nonsupplemented children. Growth over 4-mo intervals was reduced if diarrhea occurred in the first 2 mo of the interval but there were no long-term effects of apathy, fever, or anorexia. Some of the effects of morbidity on growth were therefore transient and morbidity is unlikely to be a major cause of growth retardation in this population.


Effects of dietary cholesterol, type of fat, and sex on bile lipid composition of adult baboons.

We measured the effects of dietary cholesterol (0.24 vs 0.0024 mg/kJ), type of dietary fat [saturated, a ratio of polyunsaturated to saturated fatty acids (P:S) of 0.37, vs unsaturated (P:S of 2.2)], and sex on biliary lipid and bile acid conjugate composition of 80 adult pedigreed baboons. From these data we calculated the bile cholesterol saturation index and the bile acid hydrophobicity index. Dietary cholesterol significantly increased the bile cholesterol concentration by 25% and the bile cholesterol saturation index by 15%, but did not significantly affect the bile acid conjugate composition or the bile acid hydrophobicity index. Diets high in saturated fatty acid compared with unsaturated fatty acid significantly decreased the bile cholesterol concentrations by 26% and the saturation index by 23%. Saturated fatty acid also decreased the proportion of hydrophobic bile acids and lowered the bile hydrophobicity index. Male baboons had a higher cholesterol saturation index and a lower hydrophobicity index than females. Dietary cholesterol and saturated fatty acid independently influence the bile lipid composition and the cholesterol saturation index.


Phenylalanine and tyrosine kinetics in relation to altered protein and phenylalanine and tyrosine intakes in healthy young men.

Plasma phenylalanine (Phe) and tyrosine (Tyr) turnover and the rate of conversion of phenylalanine to tyrosine (Phehyd) and of phenylalanine oxidation (Pheox) after reduced intakes of Phe and Tyr were determined in a metabolic study involving five healthy young adult men. In a pilot study, six postabsorptive young men received either 12- or 4-h infusions of [2H2]Phe and [1-13C]Tyr or [1-13C]Phe and [2H2]Tyro. From these results a primed 8-h constant infusion of [1-13C]Phe and [2H2]Tyr and [2H3]leucine was used in the metabolic study (first 3 h fasted, the 5 h fed) at the end of 1-wk periods during which subjects received an adequate nitrogen L-amino acid based-diet followed by a restricted intake of Phe and Tyr. This procedure was again repeated after 1 and 3 wk when subjects were given a diet low in both nitrogen and Phe and Tyr. Phe and Tyr fluxes were not significantly affected by diet during the fasted metabolic state but Tyr fluxes were lower when the restricted intakes were given. Compared with the rate during the fasting state, Pheox was significantly higher (P less than 0.01) when the adequate diet was consumed; Pheox and Phehyd for fed and fasted states were similar when Phe and Tyr were restricted.


Riboflavin requirements and exercise adaptation in older women.

The effects of exercise training on riboflavin requirements and of riboflavin intake on endurance were examined in 14 women, 50-67 y of age, who participated in a 10-wk, two-period crossover exercise study at two riboflavin intakes, 0.15 micrograms/kJ (0.6 micrograms/kcal) and 0.22 micrograms/kJ (0.9 micrograms/kcal). Subjects exercised 20-25 min/d, 6 d/wk, for 4-wk periods on a cycle ergometer at 75-85% of their maximal heart rate. Riboflavin status was assessed by measuring the erythrocyte glutathione reductase activity coefficient (EGRAC) and urinary riboflavin excretion. Physical performance was evaluated by using a walking treadmill test to determine maximal oxygen capacity (VO2max) and anaerobic threshold by gas exchange (ATGE). Exercise significantly affected riboflavin status as EGRAC increased (P less than 0.001) and riboflavin excretion decreased (P less than 0.01) in both groups. VO2max increased significantly with exercise (P less than 0.01). However, changes in VO2max (L/min) and ATGE with exercise training were not different in the two groups. Riboflavin requirements of older women increased with exercise training, but increased riboflavin intake did not enhance improvements in endurance.


Effect of iron on serum 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations.

In 13 of 17 infants (aged 10.5 +/- 4.3; mean +/- SD mo) with iron-deficiency anemia, the serum 24,25-dihydroxyvitamin D concentration was below the normal range and in 9 of these 13 the serum 25-hydroxyvitamin D concentration was below the normal range despite the fact that these infants received 10 micrograms vitamin D/d from the age of 1 mo. The infants were treated with intramuscular iron dextran (Imferon). The iron-dextran treatment increased the hemoglobin and serum iron concentrations as well as 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations. It is known that iron deficiency impairs fat and vitamin A intestinal absorption. Therefore, it is suggested that absorption of vitamin D may also be impaired. This may contribute to the development of vitamin D deficiency. Iron supplementation may have improved the absorption of vitamin D in the small intestine and hence increased the vitamin D concentration in the plasma.


Serum 25-hydroxyvitamin D: distribution and determinants in the Swiss population.

The serum 25-hydroxyvitamin D [25(OH)D] concentration was measured in a representative sample of the general adult population in Switzerland (n = 3276). The median concentration was 46 nmol/L and no significant difference was found between men and women. Between the ages of 25 and 74 y, 25(OH)D was not significantly correlated with age (r2 = 0.01). Six percent of the population was vitamin D deficient [ie, 25(OH)D less than or equal to 20 nmol/L] and between 34% and 95% had a relatively low concentration of vitamin D (ie, less than 38 or less than 95 nmol/L, respectively). Among the determinants of low 25(OH)D were indicators of little sunshine exposure, such as the winter season [odds ratio (OR) 2.4, 1.5-3.7 (95% confidence interval)] and less than 30 min of time spent outdoors daily by individuals greater than 65 y of age (OR 5.6, 1.5-21.2), as well as indicators of low nutritional intake of vitamin D, such as the absence of regular intake of butter or margarine (OR 2.0, 1.3-3.1) and the consumption of few dairy products (OR 1.7, 1.2-2.4).


Studies on the application of the relative-dose-response test for assessing vitamin A status in older adults.

We investigated the time course and the reproducibility of the relative-dose-response (RDR) test for assessing vitamin A status in older adults. The maximum plasma retinol response to 480 retinol equivalents (RE) of retinyl palmitate in abnormal responses was at 6 or 7 h after dosing compared with the 5-h sampling interval recommended by others for younger adults and children. With respect to reproducibility, the diagnostic concordance of two RDR tests at 7-d intervals in 14 elders was 71%. In 29% of tests, one test was abnormal and the other normal. Linear regression of the two RDR values in these 14 subjects gave a correlation coefficient of -0.08. We conclude that the procedure for the RDR should be modified when applied to persons greater than 60 y of age, and that multiple repetitions of the test are needed to provide a stable indication of vitamin A stores in an elderly individual.


Vitamin B-6 status of breast-fed neonates: influence of pyridoxine supplementation on mothers and neonates.

Vitamin B-6 concentrations in human milk are known to respond rapidly to changes in maternal vitamin B-6 intake. In this study, mothers were supplemented during the first 28 d of lactation with 2 or 27 mg pyridoxine (PN)-HCl/d and a subgroup of breast-fed infants of the 2-mg/d-supplemented mothers were supplemented with 0.4 mg PN-HCl/d. Vitamin B-6 intakes of breast-fed infants reflected the amount of their mother's supplement; intakes were highest for the vitamin-supplemented infants. Vitamin B-6 intake of mothers was a strong indicator of infant vitamin B-6 status. Vitamin intake of infants correlated significantly with five measures of vitamin B-6 status. Plasma pyridoxal-5'-phosphate (PLP) concentrations and birth weight were the strongest predictors of infant growth that were examined. Alkaline phosphatase activity in the mother's milk and infant plasma reflected pyridoxal-PLP ratios in these fluids, suggesting that the enzyme acts in regulating circulating vitamer concentrations.


Concentrations of the water-soluble vitamins thiamin, ascorbic acid, and folic acid in serum and cerebrospinal fluid of healthy individuals.

Thiamin, thiamin monophosphate, ascorbic acid, and folic acid were determined in serum and cerebrospinal fluid (CSF) in 31 outpatients who underwent a myelography because of back-pain. All subjects were otherwise healthy. The CSF concentration (mean +/- SD) was 8.6 +/- 3.9 nmol thiamin/L, 16.9 +/- 8.3 nmol thiamin monophosphate/L, 133 +/- 58.8 mumol ascorbic acid/L, and 44.9 +/- 13.2 nmol folic acid/L. The CSF-serum ratio was 2.1 +/- 0.8 for thiamin, 8.3 +/- 4.3 for thiamin monophosphate, 3.0 +/- 1.4 for ascorbic acid, and 3.3 +/- 0.8 for folic acid; the amount in CSF was significantly higher than in serum for each compound. These results support the existence of a saturated transport mechanism of water-soluble vitamins from serum into CSF for thiamin monophosphate, ascorbic acid, and folic acid. However, low CSF concentrations are correlated with low serum concentrations for the three vitamins. High serum concentrations should therefore be advocated to ensure high CSF concentrations.


Estimated mineral intakes of toddlers: predicted prevalence of inadequacy in village populations in Egypt, Kenya, and Mexico.

Intakes of minerals and factors that might affect their bioavailability were estimated for 255 toddlers aged 18-30 mo living in villages in Egypt, Kenya, and Mexico. Mean intakes over 1 y were compared with international-requirement estimates by using a probability approach. The prevalence of iron intakes likely to be inadequate to prevent anemia was estimated as 35% in Egypt, 13% in Kenya, and 43% in Mexico. The prevalence of zinc intakes likely to be inadequate to meet basal requirements was estimated as 57% and 25% in Kenya and Mexico, respectively, but only 10% in Egypt, where the use of yeast-leavened breads was judged to have improved zinc availability. There was no suggestion that estimated copper or magnesium intakes were inadequate, but calcium intakes in Kenya and Egypt were well below recommended amounts. Studies of factors affecting mineral bioavailability in the diets of these countries' populations could suggest dietary changes that might improve effective mineral intake with minimal cost.


Soy protein, phytate, and iron absorption in humans.

The effect of reducing the phytate in soy-protein isolates on nonheme-iron absorption was examined in 32 human subjects. Iron absorption was measured by using an extrinsic radioiron label in liquid-formula meals containing hydrolyzed corn starch, corn oil, and either egg white or one of a series of soy-protein isolates with different phytate contents. Iron absorption increased four- to fivefold when phytic acid was reduced from its native amount of 4.9-8.4 to less than 0.01 mg/g of isolate. Even relatively small quantities of residual phytate were strongly inhibitory and phytic acid had to be reduced to less than 0.3 mg/g of isolate (corresponding to less than 10 mg phytic acid/meal) before a meaningful increase in iron absorption was observed. However, even after removal of virtually all the phytic acid, iron absorption from the soy-protein meal was still only half that of the egg white control. It is concluded that phytic acid is a major inhibitory factor of iron absorption in soy-protein isolates but that other factors contribute to the poor bioavailability of iron from these products.


Factors affecting bone density in young adults.

A 14-y follow-up of 581 children who took part in a randomized controlled trial of the effect of a milk supplement on growth of children was conducted to investigate the supplement's effect on adult bone mineral content (BMC) and density (BMD). BMC and BMD of the nondominant forearm were measured by single-photon absorptiometry in 371 subjects (64%) aged 20-23 y, at a proximal site (shaft of radius and ulna) and at a distal site near the wrist. BMCs and BMDs tended to be higher in the intervention group (NS). Cross-sectionally, BMD was positively associated with body weight (P less than 0.01) in both sexes; inversely associated with alcohol consumption (P less than 0.05), and positively with manual occupation (NS) in men; positively associated with current intakes of calcium (P less than 0.05), vitamin D (P less than 0.01), and sports activity during adolescence (P less than 0.01), and inversely with parity (NS) in women. In multiple linear-regression analysis body weight and sports activity during adolescence were stronger determinants of female BMD than was diet.


Optimal daytime feeding regimen to prevent postprandial hypoglycemia in type 1 glycogen storage disease.

To determine the optimal daytime dietary regimen for type 1 glycogen storage disease (GSD), we used uncooked cornstarch (UCS) at a basal glucose production rate (GPR) in single and divided doses, with mixed meals at 0700 and 1700 h. This regimen was compared with a 1.5 times larger single dose of UCS at 0700 h, and with dextrose at GPR at 1200 h. Two-hour UCS loads (amount equal to GPR in 2 h) given with a mixed meal at 0700 h and 180 min later maintained mean blood glucose (BG) concentrations at greater than or equal to 4.2 mmol/L for 300 min. BG was significantly greater from 240 to 300 min compared with a single 4-h UCS load, and at 300 min compared with a single 6-h UCS load. Similar effects were noted when the divided UCS regimen was given with a mixed meal at 1700 h, but not when isoenergetic amounts of dextrose were given on the same schedules with a mixed meal at 1200 h. A daytime schedule of six UCS feedings (with the three main meals and 180 min later) at GPR maintains BG at concentrations that should minimize biochemical abnormalities and optimize clinical outcome in patients with GSD.


Parent-child relationships in nutrient intake: the Framingham Children's Study.

Nutrient intake affects many of the identified risk factors for coronary heart disease (CHD). Although CHD risk factors have been shown to aggregate within families, less is known about the familial aggregation of nutrient intake. We analyzed diet records for an average of 9 d per subject on 87 mothers, 83 fathers, and 91 children aged 3-5 y. A statistically significant but modest correlation (r less than 0.50) was found between parents' and children's intakes for most nutrients. The intake of nutrients was more strongly related between mothers and children than between fathers and children, and there was a stronger association with children's values for parents consuming more meals at home. The results of this study confirm that parents' eating habits have an impact on the nutrient intake of their preschool children; the study furnishes indirect support for dietary-intervention programs targeting families for the primary prevention of CHD.


Effect of interleukin-1, tumor necrosis factor-alpha, and interferon-alpha on the blast cells of acute myeloblastic leukemia.

In this study, we further established the role of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta, tumor necrosis factor-alpha (TNF-alpha), and interferon-alpha (IFN-alpha) as regulators of proliferation of acute myeloid leukemia (AML) cells. AML cells from 8 of 15 patients incorporated high levels of 3H-thymidine (3H-TdR) in the absence of exogenous growth factors. The spontaneous DNA synthesis could be abrogated with monospecific antibodies directed toward IL-1 alpha, IL-1 beta, or TNF-alpha, as well as with antigranulocyte-macrophage colony-stimulating factor (GM-CSF). Human recombinant GM-CSF reversed the inhibitory action of each of these antibodies and reinduced DNA synthesis in AML cells. Thus, in these cases, constitutively produced IL-1 or TNF-alpha had stimulated the synthesis of GM-CSF, which resulted in GM-CSF-dependent proliferation of AML blasts. Exogenous IL-1 up-regulated the endogenous production of GM-CSF, suggesting a positive regulation of autocrine growth factor production. We also present evidence that TNF-alpha may exert both stimulative as well as inhibitory effects on DNA synthesis in AML cells. The enhancing effect of TNF-alpha was mediated through the induction of GM-CSF production, as stimulation of DNA synthesis in AML blasts could be abrogated with anti-GM-CSF antibody. A concentration-dependent inhibitory effect of TNF-alpha on 3H-TdR incorporation into AML blasts was observed only when these cells were grown in the absence of GM-CSF. Finally, we show that human recombinant IFN-alpha is a potent inhibitor of AML cell proliferation in vitro.


Regulation of transferrin receptors by iron in human erythroblasts.

We investigated the regulatory mechanism of human erythroblast transferrin receptors (Tf.R) under conditions of iron deprivation and iron loading. Treatment of erythroblasts with an iron chelator, desferrioxamine, induced an increase in surface Tf.R number associated with an elevation of biosynthetic rate and the mRNA level of Tf.R. Reduced cellular iron pool increased the Tf.R number by altering the level of mRNA, as in nonhemoglobin-producing cells. Although treatment of erythroblasts with hemin induced a decrease in the biosynthetic rate and in the level of mRNA, the number of surface Tf.R did not decrease. This phenomenon may explain the fact that a high level of serum iron has no influence on the surface Tf.R number in vivo, as we reported previously. We suggest the existence of a regulatory mechanism specific for hemoglobin-producing cells that keeps surface Tf.R expression constant despite iron loading.


Effects of normal and sickle erythrocytes on prostacyclin release by perfused human umbilical cord veins.

We compared the effects of normal (AA) and sickle (SS) erythrocytes (RBC) on endothelial cell release of prostacyclin by perfused human umbilical cord veins. Two equal-length segments of fresh umbilical cords were perfused first with serum-free Dulbecco's modified Eagle's medium (DMEM) to establish the basal prostacyclin production rate for each segment; then one segment was perfused with SS RBC and/or plasma, while the other segment was simultaneously perfused with AA RBC and/or plasma. Aliquots of perfusate were removed at intervals for measurement of the stable prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF). Basal prostacyclin production by segments from the same cord was very similar, but it varied considerably among segments from different cords. Therefore, the ratio of prostacyclin release with RBC and/or plasma to basal prostacyclin release for each segment was used to compare prostacyclin release among segments from different cords. Mean prostacyclin release was significantly higher from segments perfused with SS RBC in autologous plasma than from segments perfused with AA RBC in autologous plasma at 15, 30, and 60 min. However, no significant differences in mean prostacyclin production were observed between segments perfused with SS vs. AA RBC in DMEM or between segments perfused with SS vs. AA plasma alone. No significant correlations were observed between prostacyclin production and either the viscosity of SS and AA RBC in autologous plasma or DMEM or the adhesiveness of SS and AA RBC to cultured human umbilical vein endothelial cells. We conclude that SS RBC in autologous plasma cause increased prostacyclin release from perfused human umbilical cord veins. The perfused human umbilical cord vein system may be a useful model for comparing the response of vascular endothelium to SS and AA RBC and plasma under controlled-flow conditions.


Relationship of thrombohemorrhagic complications to endothelial cell function in patients with chronic myeloproliferative disorders.

Thrombotic and hemorrhagic disorders are common complications of the myeloproliferative disorders. Endothelial cells release both procoagulant and profibrinolytic factors, which may contribute to these hemorrhagic or thrombotic complications. The pre- and postvenous stasis levels of the procoagulant and profibrinolytic factors produced by endothelial cells were correlated with the occurrence of complications in polycythemia rubra vera (PRV) patients (n = 29) and essential thrombocythemia (ET) patients (n = 17) compared with normal patients (n = 17). Tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor (PAI) activity, von Willebrand's factor (vWF) activity and antigen (vWF:Ag), and factor VIII activity were measured. The resting tPA activity was significantly higher in the two disease groups compared with normal controls, but no difference between the levels of tPA and either complication within the disease groups was observed. Significantly elevated tPA following venous stasis was observed in the patients of both disease groups who had bleeding complications. Significant decreases, compared with the normal group, in both resting and postvenous stasis levels of PAI were observed in the disease groups regardless of complication history. The subjects from both disease groups with thrombotic complications had significantly elevated resting vWF and both resting and postvenous stasis vWF:Ag levels compared with normal controls. The endothelial cell is likely to be responding to abnormal hemostasis rather than being primarily involved in the genesis of a hyper- or hypocoaguable state.


Enhanced platelet reactivity and hypercoagulability in the steady state of sickle cell anaemia.

A prospective controlled study was undertaken to investigate the haemostatic and coagulation status of 18 adult subjects in the steady state of sickle cell anaemia (SCA), using a relatively new in vitro technique. Shear induced haemostasis, whole blood dynamic coagulation, and spontaneous thrombolysis were measured using nonanticoagulated blood. As expected, the haemoglobin levels were significantly lower and platelet counts significantly higher in subjects with SCA compared with controls. Haemostasis and coagulation were significantly enhanced in SCA. No correlation was found between the raised platelet count and enhanced haemostasis or the reduced haemoglobin and hypercoagulation, respectively. Hyperactivity of the haemostatic system may have a pathogenic role in vaso-occlusive microthrombotic events and in the leg ulcers, both of which occur frequently in SCA.


New variant of cytochrome b5 reductase deficiency (b5RKurashiki) in red cells, platelets, lymphocytes, and cultured fibroblasts with congenital methemoglobinemia, mental and neurological retardation, and skeletal anomalies.

A Japanese man with cytochrome b5 reductase (b5R) deficiency in various blood cell lineages (red cells, platelets, and lymphocytes) and in cultured fibroblasts demonstrated congenital methemoglobinemia associated with mental and neurological retardation, and various skeletal anomalies, such as spondylosis deformans and finger joint deformations, which have never been described in association with this enzyme deficiency. Cytochrome b5 reductase deficiency was most severe in red cells (0.3-4%) and less marked in platelets (13-27%), lymphocytes (18-31%), and fibroblasts (50%). The present case appears to be a new variant of cytochrome b5 reductase deficiency (b5RKurashiki).


Spanish Rhnull family caused by a silent Rh gene: hematological, serological, and biochemical studies.

Another example of rare red cells that failed to react with all anti-Rh and anti-LW antibodies was discovered in a Spanish woman suffering from a severe hemolytic anemia typical of the Rhnull syndrome. Family study and Rh blood typings demonstrated clearly that the proposita was homozygous for a silent Rh gene complex (Rhnull of the amorph type) that she inherited from her parents who are first cousins. Western blot analysis carried out with glycosylation-independent antibodies directed against the Rh polypeptide and the LW glycoprotein, respectively, confirmed that these protein components were absent from the red cells of the proposita. In addition, the patient was typed U-positive, again in agreement with the presence on her red cells of 45-75 kDa glycoproteins detected with the murine monoclonal antibody 2D10.


Presence of an African beta-globin gene cluster haplotype in normal chromosomes in Sicily.

African admixture in Sicily has been long suspected because of the presence of the sickle gene. Nevertheless, the degree of African admixture cannot be derived from the study of HbS frequency, since this gene was most likely expanded by the selective pressure of malaria, for a long time endemic to the region. We have examined 142 individuals from the Sicilian town of Butera (12% sickle trait) to search for other markers of the globin gene cluster less likely to be selected for by malaria. The TaqI polymorphism in the intervening sequences between the two gamma genes is informative. We have found only two instances of this African marker (TaqI(-)) among 267 normal chromosomes, demonstrating that the admixture occurred at a much lower level than previously thought.


Myelodysplastic syndromes and malignant solid tumors: analysis of 21 cases.

We studied the association between myelodysplastic syndromes (MDS) and malignancies in a cohort of 155 patients with MDS, 21 of whom presented malignant solid tumors. Myelodysplasia was present after the diagnosis of cancer in eight patients (interval between the diagnosis of both conditions 18 months, median survival 49.5 months), simultaneously with diagnosis in 11 (median survival 8 months), and before malignancy in two patients (interval between the diagnosis of both conditions 47 and 7 months). One patient was given chemotherapy for lung cancer, and three patients received radiotherapy for adenocarcinoma of the kidney and cancer of the prostate. At the time of diagnosis of MDS, nine patients already presented metastatic spread. Fourteen patients died, ten as a result of tumor-related complications and four because of transformation to acute nonlymphocytic leukemia. The analysis of the incidence of malignancy in patients with MDS was statistically significant for males, and the relative risk was significant in both sexes. The results of this study show that MDS patients present a higher incidence of malignant tumors than the general population, that MDS may be of real paraneoplastic significance, and that the occurrence of MDS in cancer patients may be considered to be related to the malignancy rather than an independent phenomenon.


Splenectomy vs. alpha interferon: a randomized study in patients with previously untreated hairy cell leukemia.

Twenty patients with previously untreated hairy cell leukemia were randomized to undergo either splenectomy or to receive interferon alfa-N1, a highly purified natural alpha interferon, as primary therapy. A response in the peripheral blood elements to a hemoglobin greater than 110 gm/l, a granulocyte count greater than 1 x 10(9)/l, and a platelet count greater than 100 x 10(9)/l (Catovsky criteria) was noted in all ten patients receiving alpha interferon but in only three of the patients undergoing splenectomy (P = less than .01). Median time to response was longer in the ten interferon patients (153 days) than in the three splenectomy responders (20 days). Median time to treatment failure was significantly greater in the alpha interferon patients (greater than 18 months) than in the splenectomy patients (less than 1 month). Survival was no different since patients relapsing following splenectomy subsequently responded to alpha interferon. A significant decrease in leukemic bone marrow infiltration was observed in seven of ten patients receiving alpha interferon and in none of the patients undergoing splenectomy. Side effects, primarily infections, were more frequent in patients receiving interferon. Alpha interferon is preferable to splenectomy as initial treatment for hairy cell leukemia.


Epidemiology of AIDS in females with hemophilia and other chronic bleeding disorders in the United States: comparisons with males with chronic bleeding disorders and AIDS and with nonhemophilic female blood-transfusion recipients with AIDS.

From January 1, 1981 through June 30, 1990, 32 females with chronic bleeding disorders were diagnosed with acquired immunodeficiency syndrome (AIDS) in the United States. Most (81.3%) were white and greater than or equal to 30 years of age, with a median age of 37.5 years. Eighteen (56.3%) had von Willebrand's disease. Pneumocystis carinii pneumonia was reported for 16 (50%). None had Kaposi sarcoma. The median survival time was 10.8 months, with a cumulative probability of survival at 1 year of 47.3% and at 2 years of 27.6%. We compared the demographic data and survival times of these females with those of males with a chronic bleeding disorder and AIDS, and with those of nonhemophilic females with AIDS whose exposure to the human immunodeficiency virus (HIV) was through receipt of blood transfusions, blood components, or tissue. The principal demographic difference was age distribution. The females with chronic bleeding disorders tended to be younger than the transfused, nonhemophilic females, but older than the males. The survival time from AIDS diagnosis to death for the females with chronic bleeding disorders did not differ statistically from that of the other two groups, although older nonhemophilic females whose exposure was transfusion may progress more rapidly to AIDS.