Showing papers by "University of Barcelona published in 1991"

Severe community-acquired pneumonia. Epidemiology and prognostic factors.

Abstract: Over a period of 4 consecutive yr, 92 nonimmunosuppressed patients (21 women and 71 men aged 53 +/- 16 yr, means = SD) with critical acute respiratory failure (PaO2/FiO2, 209 +/- 9 mm Hg) caused by severe community-acquired pneumonia were admitted to the respiratory intensive care unit (RICU) of a general hospital. The most frequent underlying clinical condition was chronic obstructive pulmonary disease (44 patients, 48%). A total of 56 patients (61%) required mechanical ventilation for a mean period of 10.7 +/- 12.5 days, 29 of them (52%) needing PEEP (9.9 +/- 3.8 cm H2O). A group of 23 (25%) patients had criteria of adult respiratory distress syndrome (ARDS). A causal microorganism was identified in 48 patients (52%), the two most frequent etiologies being Streptococcus pneumoniae (14, 15%) and Legionella pneumophila (13, 14%). Pseudomonas aeruginosa (5, 5%) was always associated with bronchiectasis. Mortality due to severe community-acquired pneumonia was 22% (20 patients). According to univariate analysis, mortality was associated with anticipated death within 4 to 5 yr, inadequate antibiotic treatment before RICU admission, mechanical ventilation requirements, use of PEEP, FIO2 greater than 0.6, coexistence of ARDS, radiographic spread of the pneumonia during RICU admission, septic shock, bacteremia, and P. aeruginosa as the cause of the pneumonia. Further, recursive partitioning analysis selected two factors significantly related to the prognosis: the radiographic spread of the pneumonia during RICU admission and the presence of septic shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Life expectancy of patients with chronic nonleukemic myeloproliferative disorders.

Abstract: This study determines, within the frame of current therapeutic possibilities, the impact of chronic nonleukemic myeloproliferative disorders on expected survival. The survival data for 1067 patients (454 with polycythemia vera, 247 with essential thrombocythemia, and 366 with idiopathic myelofibrosis) were collected from 38 Spanish institutions. The actuarial survival probability of each group of patients was compared with that of the age-matched and sex-matched control population. The survival of the patients with polycythemia vera and essential thrombocythemia did not differ from that of the control population (P = 0.92 and, 0.22, respectively), whereas the survival of the patients with idiopathic myelofibrosis was strikingly reduced with respect to the control population (P = 0.0000000007). Thus, in terms of survival, current therapeutic procedures may be considered as quite satisfactory in patients with polycythemia vera and essential thrombocythemia. On the other hand, due to poor survival of patients with idiopathic myelofibrosis, new therapeutic approaches for this condition are clearly needed.

Evaluation of vancomycin for therapy of adult pneumococcal meningitis.

Abstract: The emergence of pneumococci resistant to penicillin and other agents prompted us to evaluate intravenous vancomycin for the therapy of pneumococcal meningitis, which has an overall mortality of 30%. Eleven consecutive adult patients with cerebrospinal fluid (CSF)-culture-proven pneumococcal meningitis and positive initial CSF Gram stain were given intravenous vancomycin (usual dosage, 7.5 mg/kg every 6 h for 10 days). The MBCs of vancomycin ranged from 0.25 to 0.5 micrograms/ml. Early adjunctive therapy with intravenous dexamethasone, mannitol, and sodium phenytoin was also instituted. After 48 h of therapy, all 11 patients showed a satisfactory clinical response, although the CSF culture remained positive in one case; median trough CSF and serum vancomycin levels were 2 and 5.1 micrograms/ml, respectively, and trough CSF bactericidal titers ranged from less than 1:2 to 1:16. On day 3, one patient died of acute heart failure. Four patients had clinical failure at on days 4 (two patients), 7 (one), and 8 (one) of therapy; they all immediately responded to a change in antibiotic therapy. The remaining six patients were cured after 10 days of vancomycin therapy. At this point, median peak CSF and serum vancomycin levels were 1.9 and 18.5 micrograms/ml, respectively. A transient alteration of renal function occurred in two patients, and persistent slight hypoacusia occurred in three patients. In summary, 11 adults with pneumococcal meningitis were treated with vancomycin and early adjunctive therapy including dexamethasone. All patients initially improved, and 10 were ultimately cured of the infection. However, four patients experienced a therapeutic failure, which led to a change in vancomycin therapy.

Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study.

Abstract: Objective To investigate whether isosorbide-5-mononitrate (Is-5-Mn) given with propranolol reduces hepatic portal pressure more than does propranolol alone in patients with cirrhosis. Design A randomized controlled trial. Patients Fifty patients with cirrhosis and esophageal varices entered and 42 completed the study. Intervention Twenty-one patients received oral propranolol at increasing doses until their resting heart rate was reduced by 25%, and 21 patients received oral propranolol (on the same schedule) plus oral Is-5-Mn, 40 mg twice a day. Measurements Hepatic vein pressure gradient, liver function, and splanchnic and systemic hemodynamics before and after 3 months of continuous therapy. Main results At 3 months, the hepatic venous pressure gradient decreased more (P less than 0.01) in patients given propranolol plus Is-5-Mn (19%, from 18.4 +/- 3.9 to 14.9 +/- 3.8 mm Hg; 95% CI, -2.4 to -4.5 mm Hg) than in those given propranolol alone (10%, from 18.2 +/- 3.5 to 16.3 +/- 3.1 mm Hg; CI, -1.1 to -2.7 mm Hg). The hepatic venous pressure gradient decreased by more than 20% of the baseline value in 10% of patients receiving propranolol, but in 50% of patients receiving combined therapy (P less than 0.02). There were statistically significant decreases in hepatic blood flow and the intrinsic clearance of indocyanine green after propranolol therapy, but not after combined therapy. The treatments caused similar reductions in azygos blood flow and cardiac output. Conclusions The long-term combined administration of propranolol plus Is-5-Mn reduces portal pressure more than propranolol alone without adverse effects on hepatic perfusion and liver function. Whether this greater hemodynamic effect translates into better clinical efficacy should be determined in randomized controlled trials.

Mechanisms of gas-exchange impairment in idiopathic pulmonary fibrosis.

Abstract: To investigate the mechanisms of pulmonary gas-exchange impairment in idiopathic pulmonary fibrosis (IPF) and to evaluate their potential relationship to the CO diffusing capacity (DlCO)> we studied 15 patients with IPF (mean DlCO, 52% of predicted) at rest (breathing room air and pure O2) and during exercise. We measured pulmonary hemodynamics and respiratory gas-exchange variables, and we separated the ventilation-perfusion (a) mismatching and O2 diffusion limitation components of arterial hypoxemia using the multiple inert gas elimination technique. At rest a/ mismatching was moderate (2 to 4% of cardiac output perfusing poorly or unventilated lung units), and 19% of AaPO2 was due to O2 diffusion limitation. During exercise a/ mismatch did not worsen but the diffusion component of arterial hypoxemia increased markedly (40% AaPO2, p < 0.005). We observed that those patients with higher pulmonary vascular tone (more release of hypoxic pulmonary vasoconstriction) showed less pulmonary hypertension during ...

Extracellular levels of adenosine and its metabolites in the striatum of awake rats: inhibition of uptake and metabolism

Abstract: The level of purines in the striatum of awake, freely moving rats was studied using microdialysis. The calculated extracellular concentration of adenosine and its metabolites inosine and hypoxanthine was very high immediately after implantation of the dialysis probe but decreased within 24 h to a level which remained stable for two days. Using in vitro calibration to determine the relative recovery of the dialysis probes we estimated resting levels in the striatal extracellular space to be 40, 110 and 580 nm, respectively. Inhibition of adenosine deaminase by deoxycoformycin produced a significant 1.4-fold increase in extracellular adenosine levels and a fall in inosine and hypoxanthine. A combination of three uptake blockers (dipyridamole, lidoflazine and nitrobenzylthioinosine), caused a 4.5-fold increase in extracellular adenosine levels without any change in inosine or hypoxanthine levels. After uptake inhibition deoxycoformycin did not have any significant effect. The present results show that the microdialysis technique can be used to determine levels of purines in the extracellular fluid of defined brain regions in awake animals. The high levels recorded during the first several hours after implantation may be artefactually high and reflect trauma. The results also show that adenosine levels can be altered in vivo by inhibitors of adenosine transport and adenosine deaminase. The present results indicate that the physiological adenosine level in striatal extracellular space is in the range 40–460 nm.

Potential of mean force by constrained molecular dynamics: A sodium chloride ion-pair in water

Abstract: The constrained molecular dynamics simulation method has been used to obtain the mean force and the mean force potential between two particles in solution. The method has been tested for a Lennard-Jones liquid and applied to the study of a Na+-Cl− ion-pair in aqueous solution. A flexible SPC model for water has been assumed. The results have been interpreted in the light of the solvent structure around the ions for separations corresponding to the maxima and minima of the mean force potential. In contrast to earlier studies using rigid water models, the solvent separated ion pair configurations are more stable than the contact ion pair configurations.

Acute Transformation in Nonleukemic Chronic Myeloproliferative Disorders: Actuarial Probability and Main Characteristics in a Series of 218 Patients

Abstract: In a series of 218 subjects diagnosed as having nonleukemic chronic myeloproliferative disorders in a single institution within a 18-year period, 13 instances of acute transformation were registered.

Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission.

Abstract: ▪ Objective: To compare efficacy of intensive postremission chemotherapy with allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia (ALL) in first remission. ▪ Design: ...

Loss of heterozygosity of p53 gene and p53 protein expression in human colorectal carcinomas.

Abstract: The p53 gene is a tumor suppressor gene located on chromosome 17p. Deletions of this chromosome and point mutations of p53 have been implicated in the development of colonic neoplasms. We have analyzed the loss of heterozygosity of the human p53 tumor suppressor gene in 40 cases of colorectal carcinoma using two restriction fragment length polymorphisms detected by Bg /II and Acc II restriction enzymes. p53 gene product expression was studied immunohistochemically in 64 colorectal carcinomas, 18 adenomas, and 40 normal colonic mucosae using an anti-human p53 monoclonal antibody (Pab 1801) and the avidinbiotin-peroxidase complex technique. Twelve of the 40 patients (30%) were polymorphic for the p53 gene. In ten of these informative patients (83%), the tumor samples showed the loss of one allele when compared with normal colorectal samples of the same patient. One of the homozygous patients showed a loss of both p53 alleles. p53 immunostaining was observed in 43 of 64 carcinomas (67%) but only in two adenomas (11%). These two positive adenomas showed areas of carcinoma in situ . The normal mucosa was always negative. No relation could be found between p53 immunostaining and the degree of differentiation, the extension of the tumor, or the Ki-67 proliferative index. Mucinous carcinomas and right-side carcinomas were less p53 immunoreactive (25% and 52%, respectively) than the usual adenocarcinomas (73%) and distal tumors (72%). These findings suggest that p53 may be a target of chromosome 17 deletions and that this gene may play a role in the malignant transformation of adenomas. Bg /II and Acc II restriction fragment length polymorphism analysis of the p53 gene may be a useful and direct technique to detect allelic loss of this gene in tumors.

Prognostic implication of anti-neutrophil cytoplasmic autoantibodies with myeloperoxidase specificity in anti-glomerular basement membrane disease.

Abstract: Anti-neutrophil cytoplasmic autoantibodies (ANCA) were detected in 12 out of 37 (32%) serum samples from patients with anti-glomerular basement membrane (GMB) disease by an indirect immunofluorescence assay. In 11 cases, ANCA were directed against myeloperoxidase, as revealed employing neutrophils devoid of this enzyme as the test substrate. Patients having both ANCA and anti-GBM antibodies (AGBMA) were considerably older (mean age 59 years) than patients with AGBMA alone (mean age 33 years). In addition, patients with both antibodies had some clinical and pathologic data that suggested an associated systemic vasculitis. This was supported by the fact that among these patients, those with highest ANCA titres recovered renal function despite being initially on hemodialysis, as opposed to those with lowest ANCA titres or AGBMA alone. In patients with both antibodies, there was an inverse relationship between AGBMA and ANCA values (p = 0.02). Moreover, the mean AGBMA level tended to be higher for patients with AGBMA alone than for those with both ANCA and AGBMA. These results suggest that, at least in some cases, there may be a contribution of an ANCA-related mechanism in the pathogenesis of anti-GBM disease. Although the exact role of ANCA in this and other diseases remains to be clarified, there is important clinical evidence that in anti-GBM disease ANCA may represent a serologic marker of good prognosis identifying a subset of patients who may recover renal function.

Systemic lupus erythematosus in the elderly: clinical and immunological characteristics.

Abstract: Systemic lupus erythematosus (SLE) predominantly affects young women in their 20s. In 40 out of 250 (16%) patients with SLE seen in our hospital disease onset occurred after the age of 50. The interval between the time of onset and diagnosis was five years in this older group compared with three years in the younger group. Arthritis, as a first symptom, was less common in the older onset group. During the follow up a lower incidence of arthritis, malar rash, photosensitivity, and nephropathy was found in the older onset group. In contrast, this group showed an increased incidence of myositis. High titres of anti-dsDNA tended to occur less often and the incidence of anti-Ro antibodies was lower in the older onset group. These features seem to distinguish patients with older onset SLE as a particular subset.

Uranium accumulation by Pseudomonas sp. EPS-5028.

Abstract: Pseudomonas sp. EPS-5028 was examined for the ability to accumulate uranium from solutions. The uptake of uranium by this microorganism is very rapid and is affected by pH but not by temperature, metabolic inhibitors, culture time and the presence of various cations and anions. The amount of uranium absorbed by the cells increased as the uranium concentration of the solution increased up to 55 mg uranium/g cell dry weight. Electron microscopy indicated that uranium accumulated intracellularly as needle-like fibrils. Uranium could be removed chemically from the cells, which could then be reused as a biosorbent.

Diastereoselective Enzymatic Aldol Additions: L‐Rhamnulose and L‐Fuculose 1‐Phosphate Aldolases from E. coli

Abstract: Aguilar Aldolases hold great promise as catalysts for organic syn- thesis, since enzyme-catalyzed c-C bond formations proceed with a high degree of enantio- and diastereoselectivity, which is rarely rivaled by classical synthetic methodology."] Partic- ularly, four complementary aldolases are known in carbohy- drate metabolism (Scheme 1) which catalyze the asymmetric addition of dihydroxyacetone phosphate (DHAP) to L-lac- taldehyde or D-glyceraldehyde 3-phosphate to generate a unique product each, namely only one of the four possible diastereomeric configurations. D-Fructose 1,6-bisphosphate

A genetic reconstruction of the history of the population of the Iberian Peninsula.

Abstract: The genetic patterns detectable in human populations of the Iberian Peninsula are shown by means of 'synthetic genetic maps', i.e. geographic maps of the highest principal components (PC) of gene frequencies. This method of analysis separates independent patterns of the genetic landscape, which hopefully represents different, major evolutionary events of the past. Among these are clines established by ancient important migrations, and local differentiations of populations due to barriers responsible for relative isolation. Only events of some magnitude from a demographic point of view, involving populations having initially definite genetic differences are detectable by the method. For this to be true, the genetic consequences of these events must not have been entirely smoothed out by later, prolonged genetic exchange between neighbours; but simulations have shown that long clines produced by major migrations can be rather stable in time. The first synthetic map, corresponding to the first PC, shows that the major difference in the Iberian Peninsula is that between people originally of Basque and non-Basque descent. The recession in time of the boundaries of the Basque-speaking area seems correlated with the progressive genetic dilution of the Basque genotype in modern populations, as we move away from the centre of the Basque area. Clearly there must have been a close relationship in the progressive loss of the Basque language and increasing genetic admixture with neighbours. Most probably, Basques represent descendants of Paleolithic and/or Mesolithic populations and non-Basques later arrivals, beginning with the Neolithic. The second synthetic map is correlated with early Neolithic infiltrations from the eastern edge of the Pyrenees. It has been shown by archaeologists that, in some areas, early Neolithics lived side by side at overlapping dates with well developed Mesolithics. The demographic impact of Neolithic farmers versus Mesolithics, and therefore their genetic influence was thus less important in the Iberian Peninsula than in Central Europe. The third synthetic map shows a correlation with the linguistic and historical duality between the Atlantic and Mediterranean fringes, which developed in the first millennium B.C. and was probably determined, to some extent, by infiltrations through the Pyrenees of the Urnfield cultural elements as well as by several other later events.

Neurokinin receptors differentially mediate endogenous acetylcholine release evoked by tachykinins in the neostriatum

Abstract: The regulation of neostriatal cholinergic function by tachykinins (TKs) has been studied by measuring endogenous ACh released from rat neostriatal slices. Septide (SEP; a highly selective substance P analog), neurokinin A (NKA), and neurokinin B (NKB) elicited endogenous ACh release in a concentration-dependent manner. The rank order in potency was the following: NKB (EC50 approximately 0.5 nM) greater than NKA (EC50 approximately 7 nM) greater than SEP (EC50 approximately 12 nM). Spantide (SPA) was less effective (39% inhibition) than [D-Arg6, D- Trp7,9, N-Methyl-Phe8]-substance P fragment 6–11 (53% inhibition) at antagonizing ACh release evoked by SEP and NKA. Smaller doses of the antagonists inhibited the effects of SEP compared to NKA, and the effects of NKB could only be antagonized by SPA. These findings suggest the involvement of the three neurokinin (NK) receptors in ACh release evoked by TKs with the following rank order: NK3 greater than NK2 greater than NK1. 6-Hydroxydopamine lesions of nigrostriatal neurons and tetrodotoxin (TTX) intoxication of striatal tissue revealed two different patterns of regulation of cholinergic function by TKs. On the one hand, SEP and NKA evoked ACh release, independently of the nigrostriatal dopaminergic system, by acting on NK1 and NK2 receptors that are probably localized on the somatodendritic field of cholinergic neurons receiving substance P terminals. On the other hand, dopaminergic terminals seem to regulate NKB neurons that modulate cholinergic neurons, because NKB-evoked ACh release decreased by 24% in the denervated striata. In addition, TTX partially blocked (50%) ACh release evoked by NKB, suggesting that NKB acts on NK3 receptors at both the nerve terminals and the somatodendritic field of cholinergic neurons.

Distribution of Aeromonas species in waters with different levels of pollution.

Abstract: Strains of Aeromonas spp. (883) were isolated from 10 stations in the north-west of Spain. Biotyping of the strains gave: 55% Aeromonas caviae, 34% A. hydrophila, 6% A. sobria and 5% Aeromonas spp. Phenotypic characters that have been claimed to be related to virulence such as haemolysis and the Voges-Proskauer reaction were detected mostly in A. hydrophila and A. sobria. The distribution of the species was significantly related to levels of faecal pollution in waters. Aeromonas caviae predominated in sewage and waters with a high degree of faecal pollution. In less polluted waters, either fresh or marine, A. caviae and A. hydrophila were almost equally distributed. In waters with low or no faecal pollution, the proportion of A. sobria to other species increased considerably.

Leishmania tropica au Maroc. III — Rôle vecteur de Phlebotomus sergenti - A propos de 89 isolats

Abstract: In a Moroccan focus of cutaneous leishmaniasis caused by Leishmania tropica, 7,907 female sandflies captured with CDC traps were dissected from summer to autumn 1989. Among species of the genus Phlebotomus, only P. sergenti harbored promastigotes. Eighty-nine strains belonging to the complex L. tropica were isolated. The frequency of vector infection was zero in June, rose to 1.3% in August, and reached 9.9% in October, which indicates that the period of high risk is at the end of the hot season. Out of 89 strains isolated, 74 were completely typed and corresponded to the following four zymodemes: MON-102 (one strain), MON-107 (56 strains), MON-122 (two strains), and MON-123 (15 strains). Only the first two were observed in humans. The distribution of zymodemes MON-102 and MON-107 was very different in humans, dogs, and the vector. In one of the sites surveyed, which was strongly dominated by MON-107, the absence of human cases involving this zymodeme suggests the existence of a wild reservoir.

Phosphorus limitation ofCymodocea nodosa growth

Abstract: Experimental nutrient (N, P, and N+P) additions to shallow (ca. 1 m)Cymodocea nodosa (Ucria) Aschers. stands growing in patches and in a continuous meadow in a Mediterranean Bay (Alfacs Bay, NE Spain) in 1988 demonstrated mid-summer growth to be strongly P-limited, as suggested by the high N:P ratios (>35) in unmanipulated plants. P additions resulted in increased leaf P content, reduced N:P ratios, and enhanced shoot growth and turnover in both populations. These effects promoted in turn a stand response, leading to increased biomass and, therefore, increased areal productivity in the plots receiving P. The stand response was largely attributable to a doubling of shoot density, indicating enhanced rhizome growth and branching.

The hha gene modulates haemolysin expression in Escherichia coli.

Abstract: Summary A mutation in the hha allele results in a large increase in the production of intracellular as well as extracellular haemolysin in Escherichia coli cells harbouring the haemolytic recombinant plasmid pANN202-312. This single gene mutation was located between 490 and 491.6kb on the physical map of the E. coli chromosome. From the DNA sequence of hha a small polypeptide of 8629 Da was predicted and was expressed in minicells. The deduced polypeptide sequence did not show significant similarities to other characterized proteins related to the regulation of gene expression in E. coli, although it was shown that the hha mutation increases cyloplasmic synthesis of haemolysin.

Efficient biodegradation of high-molecular-weight polyethylene glycols by pure cultures of Pseudomonas stutzeri.

Abstract: Biodegradation of polyethylene glycols (PEGs) of up to 13,000 to 14,000 molecular weight has been shown to be performed by a river water bacterial isolate (strain JA1001) identified as Pseudomonas stutzeri. A pure culture of strain JA1001 grew on PEG 1000 or PEG 10000 at 0.2% (wt/vol) as a sole source of carbon and energy with a doubling time of 135 or 150 min, respectively. Cultures metabolized 2 g of polymer per liter in less than 24 h and 10 g/liter in less than 72 h. The limit of 13,500 molecular weight in the size of the PEG sustaining growth and the presence of a PEG-oxidative activity in the periplasmic space indicated that PEGs cross the outer membrane and are subsequently metabolized in the periplasm. PEG oxidation was found to be catalyzed by PEG dehydrogenase, an enzyme that has been shown to be a single polypeptide. Characterization of PEG dehydrogenase revealed glyoxylic acid as the product of the PEG-oxidative cleavage. Glyoxylate supported growth by entering the cell and introducing its carbons in the general metabolism via the dicarboxylic acid cycle, as indicated by the ability of strain JA1001 to grow on this compound and the presence of malate synthase, the first enzyme in the pathway, in extracts of PEG-grown cells.

Prognostic clinicopathologic factors in cutaneous T-cell lymphoma.

Abstract: • Influence of clinicopathologic data on survival was analyzed in 43 patients with cutaneous T-cell lymphoma. The median age was 66 years; 35 were male and eight female. The extent of the disease, established according to a modification of the TNM system, was as follows: T1, three patients; T2, 15; T3,14; T4,11; N0, 15; N1,28; M0, 38; M1,5; B0, 37; and B1, six. The first treatment applied after staging was skin-limited therapy in seven patients and different regimens of systemic chemotherapy in 29. Seven patients received no treatment or only topical corticosteroids and tars. Median follow-up was 26 months. Nineteen patients died, with a median survival of 36.3 months. The prognostic value of age, sex, delay of diagnosis and staging, pruritus, number of sites of clinically enlarged lymph nodes, results of staging and TNM classification, erythrocyte sedimentation rate, peripheral blood cell count, liver function tests, serum lactate dehydrogenase levels, protein electrophoresis, presence of epidermotropism, thickness of cutaneous infiltrate, blastic cell percentage, mitotic index, cellular density, cutaneous eosinophilia, and follicular mucinosis was studied. Multivariate analysis (proportional hazard model with covariates) indicated that the major prognostic factors in patients with cutaneous T-cell lymphoma are as (1) in a clinical model, the T category of TNM classification and the serum lactate dehydrogenase value; and (2) in a clinicopathologic model, the T category of TNM classification and the thickness of cutaneous infiltrate (measured in 10 -1 mm from the granular layer to the lower limit of the infiltrate) of the clinically thickest lesion. ( Arch Dermatol. 1991;127:1511-1516)

Zinc-positive boutons in the cerebral cortex of lizards show glutamate immunoreactivity.

Abstract: Zinc-positive boutons, originating in the medial cortex of lizards, exhibit glutamate immunoreactivity. This finding supports the presumed homology between lizard zinc-positive boutons and the hippocampal mossy fibres of mammals, which are also glutamate-immunoreactive and zinc-positive.