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Objective: The aim of the present work was to determine the concentrations of iron and iron-binding proteins in the lungs of patients suffering from Pneumocystis carinii (PCP), which is crucial for justifying the treatment with iron-chelating agents in this disease., Patients and Methods: Bronchoalveolar lavage was performed in 10 HIV patients with PCP and five healthy controls. Total iron and iron-binding proteins (transferrin, ferritin and lactoferrin) were measured in acellular bronchoalveolar lavage fluid (BALF) in both groups. Iron was determined by atomic absorption spectrometry; transferrin and lactoferrin were measured using specific enzyme-linked immunosorbent assays (ELISA); and ferritin concentration was quantified by automated immunonephelometry., Results: Our findings in patients with PCP demonstrated a six- to seven-fold increase of total iron levels and an eight-fold increase of ferritin in bronchoalveolar lavage fluid when compared with controls. No significant differences were found in transferrin or lactoferrin levels. Moreover, our results suggest that this iron is non-transferrin bound., Conclusion: Non-transferrin bound iron is increased in the lower respiratory tracts of PCP patients. This finding would lend experiment support to the use of iron-chelating agents in this disease.

Background: Female carriers of the X-linked recessive disorder hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency show somatic cell mosaicism, and this may cause an increased synthesis of purines. We have examined whether urinary oxypurines could be useful for carrier diagnosis., Methods: Carrier testing was performed in 35 women belonging to 16 unrelated Spanish families with at least one subject affected by the Lesch-Nyhan syndrome (11 families, 14 patients) or the Kelley-Seegmiller syndrome (five families, six patients) by means of HPRT and adenine phosphoribosyltransferase activities in hair follicles and/or molecular studies. Plasma and 24-h urinary concentrations of hypoxanthine, xanthine and uric acid were measured while subjects were on a purine-restricted diet., Results: Mean plasma urate concentrations and 24-h urinary hypoxanthine, xanthine and uric acid excretion rates were significantly higher in 22 heterozygotes than in 13 non-carriers (P < 0.02). Daily urinary oxypurine excretion rates were also significantly higher in heterozygotes than in 12 normal women (P = 0.0011). Cumulative 5-day radioactivity excretion after [8-14C]-adenine infusion was markedly increased in 10 carrier women compared with five normal women (P = 0.0369). The sensitivity of 24-h urinary hypoxanthine and xanthine excretion rates was 86% and 77%, respectively, and the specificity 100% for both tests., Conclusion: Female heterozygotes for HPRT deficiency show an enhanced purine nucleotide degradation and purine overproduction. An elevated hypoxanthine and/or xanthine excretion rate differentiated most heterozygotes for HPRT deficiency from non-carrier women and thus could be useful for carrier diagnosis.

Objective: Ischemic stroke in children and infants is a rare condition. We present a series of 23 pediatric patients of ischemic stroke., Patients and Methods: A retrospective series of 23 patients, aged between 1 month and 13 years, diagnosed by anamnesis, clinical examination and neuroimaging. The clinical picture, neuroimaging findings, etiology, evolution and sequelae are evaluated., Results: Eighteen of the patients had an ischemic stroke in the carotid territory (78.3%) and 5 in the vertebro-basilar (21.7%). Idiopathic (30.4%), cardiopathy (21.7%) and migraine (17.4%) were the most frequent etiologies. The recovery was complete in 9 patients (39.1%). There was a death as a result of systemic complications caused by dehydration (4.3%), and 13 patients (56.6%) were disabled: 6 with hemiparesis of diverse grades, 5 with epilepsy and hemiparesis, one with epilepsy, and one with mental retardation., Conclusions: Ischemic stroke in children and infants is an unusual entity. The causes are multiple, although there is an elevated percentage of idiopathic cases. In our series, we highlight the significative percentage of vertebro-basilar strokes and the finding of three unusual etiologies in ischemic stroke in childhood, such as migraine, Mycoplasma pneumoniae infection and smallpox.

Phytophthora parasitica var. nicotianae produces a 34-kDa glycoprotein elicitor (CBEL) that is localized in the cell wall. A cDNA encoding the protein moiety of this elicitor was cloned and characterized. The deduced amino acid sequence consisted of two direct repeats of a cysteine-rich domain, joined by a Thr/Pro-rich region. Although having no general homology with published sequences, the positions of the cysteine residues in the two repeats show a conserved pattern, similar to that of the cellulose-binding domain of fungal glycanases. CBEL did not possess hydrolytic activity on a variety of glycans, but bound to fibrous cellulose and plant cell walls. In addition, it exerted a lectin-like hemagglutinating activity. Infiltration of tobacco leaves (cultivar 46-8) with this molecule elicited necrosis and defense gene expression at 150 nM. Elicitor pretreatment of this tobacco cultivar resulted in protection against subsequent inoculation with an otherwise virulent race of P. parasitica var. nicotianae. All these biological activities were exerted within a low concentration range. This is the first report that a fungal elicitor exhibits cellulose-binding and lectin-like activities. The possible implications of such a multifunctional elicitor in plant-microbe interactions are discussed.

Background: Many videokeratoscopes use mathematical formulas to calculate corneal radii; calculations depend on slope, curvature, coordinate position, or focal properties of the surface. Accuracy of each type of videokeratoscope must be evaluated. A controversy exists about whether axial or tangential methods best provide a precise description of corneal shape; therefore results with the Topcon CM-1000 using both methods were evaluated., Methods: Measurements were done on black polymethylmethacrylate (PMMA) spherical calibrated surfaces. Lenses were first aligned and measured and then misaligned in different directions and measured. Results for each position were compared with the zero or alignment position., Results: Accuracy of the CM-1000 was high even under extreme misalignment conditions. Tolerance to misalignment was high (about 300 mm). Misalignment-induced variations in the output results were small (usually less than 0.05 mm). However, important variations (more than 1.00 diopter [D]) were found for the lowest measured radius (6 mm). In some cases, small differences between axial and tangential radii for the same point could be found., Conclusion: With the exception of extremely low radii of curvature, the CM-1000 was accurate for measuring spherical surfaces. Further investigation remains to be done on aspheric surfaces and in clinical practice.

Objective: To evaluate results of the Papanicolaou cervical cytology test performed between 1986 and 1995., Design: A descriptive and retrospective study., Setting: Primary care, San Juan Health Centre, Salamanca., Participants: 1,271 women over 15 who had at least one smear during the study period., Intervention: Review of clinical histories and cytology reports., Results: 2,056 smears were carried out. 50% were on women < 35, for whom family planning was the main reason for the test. Only 31% of the women between 35 and 65 had a smear. 35% of the women recruited had a further cytology test. 56% had morphological or microbiological disorders, 43.1% were negative and only 0.9% could not be evaluated by the pathologist. There were benign morphological alterations in 48.4% and infections in 27.3%. Only 15 smears (0.7%), corresponding to 12 women (1.2%), had suspected malignity, with dysplasia confirmed in 3 cases (0.24%)., Conclusions: There were few cases of cervical cancer detected with the methods followed at our centre. The effectiveness of the intervention should be improved by selective screening based on risk scales, setting up computerised systems of identification and the extension of the interval between smears to 5 years.

ABSTRACT A glycoprotein of 34 kDa (GP 34) was solubilized at acidic pH from the mycelium of Phytophthora parasitica var. nicotianae and was purified by ion exchange and gel permeation chromatography. Whole tobacco plants treated with GP 34 through their roots showed an enhanced lipoxygenase activity as well as hydroxyproline-rich glycoprotein accumulation, indicating that this molecule had elicitor properties. An antiserum raised against the pure glycoprotein allowed localization of GP 34 by immunogold-labeling on the cell surface of the mycelium when the fungus was grown in vitro. In the wall-less zoospores, GP 34 was limited to the flagellum surface. It was then abundantly synthesized at the onset of encystment. During infection of tobacco plants, labeling was very faint at early stages of colonization, particularly in the susceptible host cultivar. It appeared earlier in the resistant host cultivar and was restricted to the living fungus, declining with mycelium cell death.

Introduction: Spontaneous or non-traumatic intracranial haemorrhages seen in children of under 15 years old are most frequently due to cerebral vascular malformations, followed at a considerable distance by blood disorders, vasculopathies, tumours and the complications of radio-therapy., Objective: To present the cases of spontaneous and non-traumatic cerebral haemorrhage seen at our hospital., Material and Methods: We reviewed all the paediatric cases of spontaneous cerebral haemorrhage diagnosed in our hospital over the previous sixteen years, excluding bleeding in the neonatal period. Computerized tomography was done in all cases, study of the cerebrospinal fluid, angiography and/or magnetic resonance in some cases., Results: We selected 44 patients, of who the aetiology could be determined in 30. Of these, 20 cases were due to vascular malformations, 7 were associated with haematological disorders, 2 with cerebral tumours and one case with meningococcal sepsis. The commonest form of presentation was that of an acute intracranial hypertension syndrome, also showing focal deficits, partial crises and meningism., Conclusions: The commonest cause of spontaneous intracranial haemorrhage in children is due to rupture of a vascular malformation, namely an arterio-venous malformation. Angiography and/or magnetic resonance are the techniques of choice for diagnosis. The various causes of disorders of haemostasia also are important in giving rise to intracranial bleeding.

We analyze changes in eosinophilic cationic protein (ECP) serum levels after treatment with intranasal corticoids. Fifty-three healthy individuals (control group) and 21 patients diagnosed of allergic rhinitis, with or without bronchial asthma, were enrolled at a time when they had only nasal symptoms. Data were collected from skin Prick tests, forced spirometry, methacholine challenge, and complete blood workups, including IgE measurement, eosinophil counts and ECP serum levels determined by immunofluorescence. The patients received intranasal budesonide at a dose of 200 micrograms/24 h. ECP levels and eosinophil counts were determined before (baseline levels) and during treatment (on days 21 and 60). We found significant differences (p < 0.01) in baseline ECP levels of the controls (9.34 +/- 5.76) and patients (16.47 +/- 15.28). These values were significantly lower than baseline 21 and 60 days after treatment, although the changes between days 21 and 60 were not significant. Eosinophil counts did not fall significantly. We also found that eosinophil counts and ECP levels were correlated (r = 0.53) at baseline but not after treatment (r = 0.25). No patient experienced bronchial symptoms during the study. We conclude that ECP serum levels in patients with symptoms of rhinitis are significantly higher than levels in non symptomatic individuals. These levels fall significantly, possibly due to intranasal corticoid treatment, although eosinophil counts remain constant. ECP levels can therefore be used to monitor inflammatory activity in patients with allergic rhinitis.

Objective: The aim of this study was to assess the use of transvaginal ultrasonography in measuring endometrial thickness in postmenopausal women with bleeding, thus to determine the least invasive treatment., Study Design: We evaluated 168 women with postmenopausal bleeding by transvaginal ultrasonography and histological study of the endometrium., Results: No cancerous or precancerous lesions were found when endometrial thickness was under 10 mm. The mean endometrial thickness in women with cancerous and precancerous lesions was 10.75 +/- 1.63 mm, while in non-pathological lesions it was 1.36 +/- 1.18 mm., Conclusions: To diagnose endometrial pathology, an endometrial thickness over 6 mm yields a sensitivity of 88.6%, a specificity of 90.6%, a positive predictive value of 92%, with 4.6% of false-positives and 4.6% of false-negatives (six small polyps and one irregular maturation). Although we are waiting for other prospective and multicentric studies, our present experience leads us to believe that Dilatation and Curettage (D&C) can be avoided in postmenopausal bleeding with endometrial thickness under or equal to 6 mm.

Primary gout is characterized by increased plasma and decreased urinary concentrations of hypoxanthine, xanthine and uric acid. To examine whether lead could explain the disturbance of purine metabolism in gout, we determined hypoxanthine, xanthine and uric acid metabolism and 5-day cumulative urinary lead excretion rates after an EDTA (calcium disodium edetate) test in 27 patients with primary gout and reduced creatinine clearance (C(cr)) and in 50 patients with gout and normal C(cr). The results were compared to those obtained in 26 normal subjects matched for age. All gout patients evidenced a marked renal underexcretion of hypoxanthine, xanthine and uric acid relative to their increased plasma levels. Purine metabolism was remarkably similar in both gout groups except for a significantly lower uric acid excretion in patients with reduced C(cr). Blood lead levels and cumulative lead excretion rates were significantly higher in gout patients with renal failure as compared to patients with normal C(cr). Fourteen patients (52%) with renal insufficiency and 6 (12%) with normal C(cr) showed increased lead excretion rates (95% Cl for the difference, 29-51%, p < 0.001). Mobilizable lead was not significantly correlated with serum or urinary purine concentrations. Hypoxanthine, xanthine and uric acid underexcretion was similar in gout patients with increased or normal cumulative lead excretion rates. The prevalence of atheromatosis and arterial hypertension together was significantly higher in gout patients with renal failure than in patients with normal C(cr) (81 vs. 60%, 95% Cl for the difference, 11-31%, p < 0.005). These results indicate that lead is not a significant contributor to the renal underexcretion of purines in gout. An increased mobilizable lead is not by itself evidence that lead is the cause of the renal insufficiency in patients with primary gout. Atheromatous nephropathy and/or nephroangiosclerosis may explain impaired renal function in patients with primary gout.

We present the results of treatment with vigabatrin in the polytherapy of resistant infantile epilepsy. A retrospective review of 55 children with resistant epilepsy aged between 2 months and 15 years was carried out between January 1992 and January 1995. Semiologically, the crises treated were simple partial crises (CPS), complex partial crises (CPC), West's syndrome, the Lennox-Gastaut syndrome and polymorphic crises. The efficacy of the drug (defined as a 50% or more reduction in crises), secondary effects and the reduction in the number of drugs necessary were evaluated. 60% of the children studied improved. 20% became completely free of crises. 34% remained unchanged and 3% became worse. In West's syndrome 100% responded satisfactorily, as did 80% of the cases of partial crises, but only 40% of those with Lennox's syndrome responded. Generalized tonic-clonic crises did not respond, and myoclonic crises became worse. Aetiologically, there was greater improvement in the symptomic cases than in the essential cases, the improvement being 70% while 5 patients with tuberose sclerosis responded particularly well. Medication was stopped in one case because of side-effects, due to a psychiatric disturbance, and in another case vigabatrin caused transitory side-effects. In 10% of the subjects the initial efficacy wore off around 6 months later. We have shown the usefulness of vigabatrin in the polytherapy of infantile epilepsy, which is resistant to conventional epileptic drugs, mainly in simple and complex partial crises and in West's syndrome. Its minimal side-effects and the favourable response in over 50% of cases make it an extremely useful drug.

Miller Fisher syndrome (MFS) is characterized by the triad of ataxia, areflexia and ophthalmoplegia. It is exceptional for infants to be involved. Two infants, aged 11 and 16 months, developed acute-onset MFS. Both patients had prodromal upper respiratory tract infection. Pupillary responses to light, strength and sensation modalities were preserved. One patient was lethargic for a day; the electroencephalogram disclosed slightly slow background activity that later became normal. The other received high-dose intravenous immunoglobulins for 5 consecutive days starting at once on admission; within the next 7 days he became asymptomatic. Increased cerebrospinal fluid protein content and delayed nerve conduction studies with prolonged distal latencies were encountered in both patients.

Tourette's syndrome (GdT) is a chronic neuropsychiatric disorder of unclear etiology characterized clinically by the presence of motor and phonic tics as well as a variety of behavioral and cognitive abnormalities such as Obsessive-Compulsive Disorder (TOC) and Attention Deficit Hyperactivity Disorder (ADHD). Dopaminergic pathway and movement control related structures may have some implications for pathogenesis. Neuroimaging techniques may yield relevant data for a better understanding of the symptoms and physiopathology of this disease. Among them, functional isotopic techniques such as PET and SPECT and other like quantitative EEG are the most remarkable. In this article we intend to perform a thorough review of the most recent literature, contributing with our own experience and discuss the pathogenesis of GdT.

Bronchoalveolar lavage (BAL) samples used to study immune or inflammatory response in interstitial lung disease must be representative of the lower respiratory tract. Thus, the selection of suitable samples must be part of routine practice. To assess the incidence of unsuitable BAL samples used for cytology and to determine the relation between parameters related to underlying disease and the quality of samples. One hundred sixty-one patients were enrolled. Seventy-two were HIV positive and had diffuse pulmonary infiltrates, 34 had idiopathic pulmonary fibrosis (IPF), 10 had sarcoidosis, 10 had hypersensitivity pneumonitis, 19 had interstitial lung disease and collagen diseases and 2 had pulmonary eosinophilia. Fourteen individuals formed the control group. The quality study was carried out by staining the BAL samples following a modified Wright-Giemsa technique and evaluating the samples by the selection criteria described by Chamberlain and colleagues (1987). We identified unsuitable samples from 53% of the HIV positive patients, from 35% of the IPF patients and from 21% of the interstitial lung disease patients with associated connective tissue disease. In the other groups, all samples were suitable for analysis. Intolerance of BAL with decreasing percentage of fluid recovered was significantly associated with sample quality, particularly in the IPF group. The cytology results that invalidated the samples differed by group. In all groups, unsuitable specimens had low cell counts. The finding or not of evidence of associated infection in HIV-infected patients, on the other hand, did not appear to determine sample quality in and of itself, although it did in samples related to other entities. We can predict that a high rate of unsuitable BAL samples will come mainly from patients with diffuse lung disease associated to HIV infection, IPF and interstitial lung disease with associated connective tissue disease. Tolerance to the technique influences quality of the specimen obtained and, therefore, should be taken into account in interpreting the findings of cytology. The criteria applied by the various teams using BAL should be unified, and it should be determined whether the exclusion of inappropriate samples affects the final composition of study groups.

We retrospectively checked 53 paediatric patients suffering from infection with human immunodeficiency virus (HIV) registered in our Centre between the years 1987 and 1993, and evaluated the appearance of HIV encephalopathy. We noted important neurological signs in eleven patients (20.7%) ten of whom had HIV infection via vertical transmission and one as a result of contamination from haemoderivatives. In this review we give a detailed description of neurological signs, the moment of onset of these signs and their possible relationship with the state of the HIV infection. We also analyzed the resulting neuroradiological findings as well as any abnormalities in cerebrospinal fluid. Follow-up period ranged from one month to two and a half years from the moment of onset of the appearance of encephalopathy. Although most of our patients showed a clear improvement after oral or intravenous treatment with zidovudine, this improvement generally proved to be short-lived. The mortality rate in our HIV encephalopathy series was 81.8%, this figure being reached two and a half years after encephalopathy. The appearance of neurological signs in HIV patients therefore represents a very gloomy prognostic factor in the evolution of the disease.

Background/aims: This study analyzed the response of two selected groups of asymptomatic chronic hepatitis B patients, treated either with Interferon or with Prednisone plus the same regimen of Interferon, on finalizing treatment and after a long-term follow-up., Patients and Methods: Twelve patients received Interferon over 6 months (group I) and 7 patients Prednisone plus Interferon with the same regimen (group II). Both groups were homogeneous in age, sexual preferences, serum ALT levels, liver histology and Knodell's index. Patients with decompensated liver disease, ongoing drug abuse, active alcoholism or viral superinfections were excluded., Results: On finalizing treatment, no statistical differences were observed in either group, except for clearance of HBsAg, found to be better in group II. Both treatments improved hepatic histology. These results were comparable with those reported for both therapeutical regimens in the literature. After a mean follow-up period of 1.8 years for group I and 3.5 years for group II, no patient included in group II relapsed and 2 additionally cleared their replication markers; thus, a complete response was achieved in 6 (86%) out of 7 patients. In group I, however, 3 patients relapsed and 4 presented no change, obtaining a complete response in 3 (27%) out of 11 followed-up patients. When statistically studied, this improved response in the Prednisone plus Interferon group was significant in clearing HBV DNA, HBeAg and HBsAg and, also, in normalizing ALT levels., Conclusions: In spite of the few number of cases studied, these results could indicate an improved long-term evolution after a short course of steroids prior to Interferon in selected chronic hepatitis B patients.

The aim of this work is to review of the role of nitric oxide (NO) in the lower respiratory tract. This review mainly focuses on the generation of nitric oxide by alveolar macrophages. In the first part of the paper, we summarize the literature on nitric oxide synthesis by different cell types and the effects of this mediator on target cells. Methods for measuring nitric oxide are also analyzed. The core of the paper is a review of the role of nitric oxide in diffuse interstitial lung diseases (both human and experimental models). We include data about the concentration of this mediator in bronchoalveolar lavage fluid and then summarize the knowledge about the regulation of nitric oxide synthesis by animal or human alveolar macrophages. Finally, we review the biological effects of nitric oxide in the lower respiratory tract.

Background/aims: Interferon can induce autoantibodies and autoimmune reactions. This study reviewed the clinical, serological, and HLA phenotypical features of patients who developed autoimmune hepatitis during interferon therapy for chronic hepatitis C, analyzing their response to immunosuppressive treatment., Methods: The diagnosis of chronic hepatitis C was based on positivity for viral RNA and a liver biopsy specimen obtained before interferon treatment. Sera were tested for autoantibodies by indirect immunofluorescence assay. HLA typing was performed by applying a standard microlymphocytotoxicity method., Results: Of 144 patients with chronic hepatitis C treated with interferon, 7 women deteriorated during treatment; serum transaminase, gamma-globulin, and immunoglobulin G levels increased; and serum autoantibodies became positive. Interferon was interrupted, a diagnosis of autoimmune hepatitis was established, and immunosuppressive therapy was initiated. All patients responded to this treatment. The 7 patients had similar HLA typing to those with autoimmune hepatitis, with DR4 in 2 patients (67%) with type 2 autoimmune hepatitis, and with DR3 and DR52 in 2 (50%) and 4 (100%) patients, respectively, with type 1 autoimmune hepatitis; additionally, 5 patients (71%) had DQ2, and 4 (57%) had both DR52 and DQ2., Conclusions: In female patients with chronic hepatitis C, a genetic susceptibility to autoimmune hepatitis may exist, possibly triggered by immunostimulating effects during interferon therapy. Immunosuppressive treatment has been well tolerated and seems to be effective.

We analyzed serum levels of eosinophilic cationic protein (ECP), one of the 4 main eosinophilic proteins; ECP is released from an activated cell and acts as a mediator of inflammation. Serum samples from 139 persons were studied prospectively. Fifty-three individuals from the general population provided the control group. Eighty-six consecutive patients were also studied: 69 with bronchial asthma and 17 with allergic rhinitis and no signs of asthma. The level of severity of disease was established in the asthmatics by the method proposed by Aas (Aas score), based on symptoms and medications received within the last year. We also classified these patients as having mild, moderate or severe asthma according to the latest criteria issued by the International Consensus for Diagnosis and Treatment of Asthma. Atopic status was estimated by skin Prick tests. ECP levels in the control group (9.34 +/- 5.76 micrograms/l) were significantly lower (p < 0.001) than those of the total population of patients (17.59 +/- 16.85 micrograms/l). The mean for patients with rhinitis was 14.76 +/- 10.94 micrograms/l, whereas it was 18.29 +/- 18 micrograms/l in the asthmatics; the levels for both groups were statistically different from that of the control group (p < 0.03 and p < 0.001, respectively). Levels by degrees of severity established at the time of revision and by sensitivity to allergens were also significantly different from the level of the control group, although the mean levels were low in the group of severely affected patients who had received treatment with inhaled corticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Unlabelled: Alterations in gait are a frequent cause of consultation in neuropaediatric units. They have several different causes. One subgroup of special interest concerns those which have their origin in a neuromuscular disease. We studied the experience of the Child Neurology Unit at the Hospital 12 October from 1980 to 1993., Material and Methods: between 1980 and 1993 a total of 176 were studied because they showed alterations in their gait caused by a neuromuscular disease. Frequency and clinical features were analysed (sex, age at the beginning of the deterioration, duration of the latter etc.)., Results and Conclusions: the alterations in gait were separated into two groups: Group I: backward or non-acquired gait. Group II: deterioration in gait. IIa: temporary. IIb: definitive. The most frequent cause in Group I was spinal muscular atrophy and in Group II, muscular dystrophy linked to sex. To sum up, muscular diseases are far more important than the neuropathic ones, except for Group IIa where acute demyelinating motor polyneuritis was to be found at the top of the list of frequent occurrences.

Meningioangiomatosis (MA) is a rare benign intracranial tumour of uncertain pathogenesis, with only 33 cases reported in the literature. Imaging features have been described in 21 cases, only 3 with contrast-enhanced MRI. We present two cases of MA with MRI and/or CT findings and gross, ultrastructural, and immunohistochemical characteristics. MRI is particularly helpful for establishing the origin of the lesion and its anatomical location, while CT shows calcification, if present. The pathological characteristics establish the diagnosis and underline the differences from other entities such as malignant meningioma, one of the most important differential diagnostic considerations.

Purpose: Uncontrolled studies have shown that women with gout have higher serum urate concentrations and similar or lower urinary uric acid excretion rates than do men with gout. These observations suggest a more defective tubular transport of uric acid in women than in men with gout. In this prospective study we assessed purine metabolism in women with primary gout under controlled conditions. We also examined whether there are sex-related differences in plasma and urinary purine concentrations among patients with primary gout., Subjects and Methods: Ten women with crystal-proved primary gout and normal serum creatinine levels (below 116 mmol/L) were studied while they were on a purine-restricted diet and taking no medications known to influence uric acid metabolism. For comparison, 20 men with primary gout and 10 women without gout, matched for age, race, and body mass index, were studied under the same conditions. In each subject, plasma and 24-hour urinary uric acid, hypoxanthine, and xanthine concentrations were measured. The mean of three consecutive determinations for plasma purines and five for urinary purines was used. Standard formulas were used to calculate the renal clearances and the fractional excretion of purines., Results: Mean plasma urate, hypoxanthine, and xanthine levels were significantly higher in women patients with primary gout compared with normal women (P < 0.05). Mean 24-hour urinary uric acid excretion was similar in both groups. Daily urinary hypoxanthine and xanthine excretion rates were significantly lower in gouty women patients than in control women (P < 0.05). The renal clearances and the fractional excretion of uric acid, hypoxanthine, and xanthine were markedly lower in women with primary gout than in control women (P < 0.05). Plasma and urinary purine concentrations were similarly increased and diminished, respectively, in women and men patients with primary gout. Plasma urate, hypoxanthine, and xanthine levels were inversely and significantly associated with the fractional excretion of uric acid (r = -0.520; P = 0.003), hypoxanthine (r = -0.555; P = 0.002), and xanthine (r = -0.384; P = 0.040), respectively., Conclusion: Women with primary gout have markedly diminished uric acid, hypoxanthine, and xanthine excretion rates. The disturbance of purine metabolism appears to be of a similar magnitude to that observed in gouty men. The absence of significant sex-related differences in plasma and urinary purine concentrations suggests a similar tubular dysfunction for purine excretion in women and men with primary gout.

Background: The hypoxanthine-guanine phosphoribosyltransferase deficiency (HGPRT) may have two clinical forms: that of the Lesch-Nyhan syndrome (complete HGPRT deficiency) and that of the Kelley-Seegmiller syndrome (partial HGPRT deficiency). The clinical and biochemical features of the HGPRT deficiency are not completely known., Methods: A series of 12 patients, 8 with the Lesch-Nyhan syndrome and 4 with the Kelley-Seegmiller syndrome are described. The plasma and urine concentrations of hypoxanthine, xanthine and uric acid were compared with those obtained in 20 normal subjects and 41 patients with primary gout. The molecular defect which determines the deficient HGPRT activity was studied in one patient with the Kelley-Seegmiller syndrome., Results: The 8 patients with the Lesch-Nyhan syndrome presented choreoathetosis, corticospinal motor system dysfunction, mental retardation and signs of self mutilation. The neurologic manifestations of the patients with the Kelley-Seegmiller syndrome were very heterogeneous: two patients had psychomotor retardation with spastic movement, one was mentally retarded with generalized dystonia and one patient only had gout with no neurologic manifestations. The erythrocytic HGPRT activity ranged between 0.28 and < 0.01 nmol/h and mg of hemoglobin in all the patients. Plasma and urine purine concentrations were very high, being greater than those in normal subjects and patients with gout (p < 0.01). A mutation was identified in exon 3 (substitution of guanine with thymine) conditioning the substitution of the normal glycine amino acid by valine (HGPRT Madrid) on molecular study., Conclusions: The hypoxanthine-guanine phosphoribosyltransferase deficiency has a heterogeneous clinical expression. The activity of this enzyme in erythrocytes and the results of the metabolism of the purines do not allow prediction of the severity of the clinical manifestations.

Skin biopsy is the method of choice for the diagnosis of Lafora's disease. The presence of PAS (+) inclusions characteristic of Lafora's disease has been thought to be more evident in aprocrine glands of the axillary skin than in the duct cells of the eccrine glands. We describe 4 patients with Lafora's disease diagnosed by axilla skin biopsy, confirming the usefulness of this procedure.

Purine nucleotides are synthesized and degraded through a regulated series of reactions which end in the formation of uric acid. Increased uric acid synthesis may be the result of two major pathophysiological disorders: increased de novo purine synthesis and enhanced purine nucleotide degradation, both of which may be the result of an increased or decreased enzyme activity. In addition, some conditions and disorders associated with uric acid overproduction have been recognized as the result of increased ATP degradation or decreased synthesis of ATP. The clinical manifestations of the diseases leading to excess uric acid synthesis are heterogenous, but symptoms related to uric acid overproduction are always secondary to the precipitation of crystals in soft tissues, joints, and the kidney excretory system. In clinical practice, serum urate concentration and urinary uric acid excretion are used to assess uric acid synthesis, taking into account that a purine-rich diet can be a confounding variable. Quantification of uric acid precursors, such as adenosine, inosine, guanosine, hypoxanthine, and xanthine, in biological fluids and intracellular nucleotides has provided further insight into the metabolic disturbances underlying disorders associated with uric acid overproduction. Additional studies are necessary to define precisely the metabolic derangement in idiopathic uric acid overproduction and to assess fully the consequences of increased purine nucleotide degradation, such as free-radical formation, increased adenosine synthesis, and reduced synthesis of signal transducers.

Methods currently employed for measurement of phosphoribosylpyrophosphate synthetase (ribophosphate pyrophosphokinase; PRPPs) activity are cumbersome and expensive, requiring an auxiliary enzyme reaction, a radioactive nucleobase and multiple incubations, or do not allow a complete kinetic study. The aim of the present study is to describe a simplified, single step, non-isotopic method for determination of PRPPs in hemolysate, appropriate for a complete screening of PRPPs activity disorders. Briefly, the charcoal-treated hemolysate is incubated with saturating amounts of substrates and P1 P5 di(adenosine 5') pentaphosphate (Ap5A), an inhibitor of human adenylate kinase, to prevent conversion of AMP to ADP. AMP generated in this reaction is then measured by HPLC. Adenylate kinase activity was fully inhibited by Ap5A, allowing the accurate determination of AMP. The method was sensitive and reproducible and mean and variance values compared closely with those reported using other, more complicated, assay procedures. The hyperbolic curve relating Pi concentration to initial reaction velocity was shifted to sigmoidal by addition of 0.02 mmol/l GDP which inhibited PRPPs activities only at inorganic phosphate concentrations < 2 mmol/l. This suggests that this method should provide sensitive and accurate screening for regulatory, as well as catalytic, defects underlying PRPPs superactivity.

A prospective randomized, double-blind, double-dummy study investigated the effects of two angiotensin converting enzyme (ACE) inhibitors on urinary albumin excretion in nondiabetic patients with mild to moderate essential hypertension. At the end of a 4-week placebo run-in period, 36 patients were randomly allocated to receive a 12-week course of treatment with quinapril (10, 20, or 40 mg) once daily or captopril (25, 50, or 75 mg) twice daily. Seventeen patients in each group completed the study. The mean change in mean blood pressure for patients taking quinapril (mean dose 32 mg/24 h) was -5 mm Hg (P = .002), and for patients taking captopril (mean dose 132 mg/24 h), -9 mm Hg (P = .002). The baseline urinary albumin excretion rate in both groups was (mean +/- EEM) 57 +/- 7 micrograms/min. Fifteen patients in the quinapril group and 12 patients in the captopril group had baseline albumin excretion rates of more than 20 micrograms/min. Mean urinary albumin excretion decreased in patients treated with quinapril from 55 to 33 micrograms/min (mean decrease 22 micrograms/min, 95% confidence interval [CI], 1 to 43 micrograms/min; P = .031) and with captopril from 59 to 41 micrograms/min (mean decrease 18 micrograms/min, 95% CI, 3 to 32 micrograms/min; P = .025). No significant modifications were observed in serum lipid concentrations, serum and urinary electrolytes, and magnesium or phosphorus metabolism. Mean urinary calcium excretion decreased in the quinapril-treated group (from 219 to 188 mg/24 h; P = .023) but not in the captopril group (from 264 to 267 mg/24 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Investigations in animals have shown that nicotinic acid, an intestinal cyclic-AMP inhibitor, partially corrects the metabolic changes associated with urinary diversion through intestinal segments. Blood and serum chemistry were studied in patients before and 3 to 5 months after undergoing urinary diversion through ileal segments, both with and without nicotinic acid treatment. It was found that diverted patients had metabolic acidosis, an increased anion gap and increased levels of serum alkaline phosphatase; there were no significant changes in serum PTH and vitamin D levels, calcaemia and phosphoraemia. There was a tendency towards dehydration, hypernatraemia, hyperchloraemia and secondary hyperaldosteronism produced by ileal secretion of a hypotonic fluid. Nicotinic acid 3 g/day significantly reduced the chloraemia but did not correct the metabolic acidosis, although it reduced its severity, since blood pH decreased when treatment was suspended. Nicotinic acid cannot be recommended for routine use in the management of metabolic acidosis after urinary diversion, and patients with a marginal renal reserve should not be considered for trans-intestinal urinary diversion.

This study was conducted to quantify urinary solute transport by the ileum, using an in vivo human model, and to determine the effect of nicotinic acid on this process. Patients were studied under both basal conditions and niacin therapy. The rates of solute transport were established by analysis of excretion indexes for each solute. Potassium and ammonium were absorbed by the ileum, while phosphorus, sodium and bicarbonate were secreted. The percentage excretion index of sodium and bicarbonate increased by approximately 100 and 600% respectively, causing a significant rise in urinary pH. Although not statistically significant, there was a tendency for chloride to be absorbed and for water to pass into the bowel lumen. Nicotinic acid 3 g/day had no significant effect on urinary solute transport.

A reduced spatial and temporal coherence light from a halogen lamp is used to copy holographic optical elements, and a maximum diffraction efficiency of 80% is achieved.

Objective: To analyze the expression of different HLA class I antigens and cell adhesion molecules on frozen liver sections from patients with chronic active hepatitis, types B and C., Experimental Design: Liver biopsy samples were divided into two parts, one for routine histological examination and another, after snap-freezing and storing at -80 degrees C, for immunohistochemical analysis. To carry out immunoperoxidase and immunofluorescence stainings, a panel of monoclonal antibodies specific for HLA class I light (beta 2-microglobulin) and heavy chain determinants, and for adhesion molecules such as intercellular adhesion molecule-1 and lymphocyte function associate antigen-3 was used., Patients: Immunohistochemistry was performed in frozen liver biopsy sections from 25 patients with viral chronic active hepatitis, 10 type B and 15 type C. As controls, normal liver samples and liver specimens from patients with cholestasis or steatosis were also studied., Results: HLA class I light and heavy chain determinants were expressed on hepatocytes, biliary duct epithelium, sinusoidal lining cells and lymphocytes from patients and controls; however, the beta 2-microglobulin conformational epitope was undetectable on hepatocytes from normal livers or with cholestasis or steatosis, but clearly positive on hepatocytes from patients with hepatitis. In addition, in liver sections from controls no adhesion molecules positivity was detected on hepatocytes; by contrast, hepatocytes from patients with hepatitis showed markedly enhanced membranous reactivity for both adhesion molecules in areas of piecemeal and lobular necrosis., Conclusions: Virus B and C infections could induce an increased hepatocellular expression of HLA-class I determinants, including the conformational epitope adequate for antigen presentation, and cell-cell adhesion molecules. These findings underline the role of cell mediated immune reactions in the pathogenesis of hepatic injury in viral chronic hepatitis.

The composition and the holographic behavior of a new photopolymer with high diffraction efficiencies (30% at 514 and 60% at 633 nm) are described.