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Biomedical subjects

J Fernandez

Publications and source records attributed to J Fernandez.

At least 73 records · Page 4Linked to original sources

Perioperative risk factors affecting hospital stay and hospital costs in open heart surgery for patients > or = 65 years old.

OBJECTIVE: Demographic changes, associated with increased demands for open heart surgery in the elderly, place increased burden on financial resources. To evaluate perioperative risk factors affecting incidence of hospital events and estimation of hospital charges, 2577 patients > or = 65 years (range 65-91), operated on from January 1991 to December 1994, were compared with a concurrent cohort of 2642 younger patients. METHODS: Statistical analysis, by surgical procedure, focused on hospital mortality, key postoperative complications affecting length of hospital stay and hospital charges. RESULTS: Overall hospital mortality was 4.7%, 3.5% in younger patients versus 6.1% in the older group (P << 0.01). Mortality was significantly lower in patients less than 65 years undergoing coronary artery bypass grafting (3% versus 5%, P < 0.01) and valve replacement (4% versus 9%, P = 0.01). Significant risk factors for hospital death in the elderly: diabetes (P < 0.01), hypertension (P < 0.01), myocardial infarction (P < 0.01) and congestive heart failure (P < 0.01). Significant postoperative events, more common in older patients, included prolonged ventilation (P << 0.01), congestive heart failure (P << 0.01), infection (P << 0.01), cerebrovascular accident (P < 0.01), and intra aortic balloon pump (P < 0.01). Incremental risk factors for morbidity in the elderly were: higher New York Heart Association class, congestive heart failure, emergent operation, and female gender. Mean length of hospital stay for the < 65 group was 15.3 versus > 19.5 days for the > 65 group (P << 0.01). Length of stay over 18 days positively correlated with increased morbidity in both age groups. For patients > or = 65 years of age, the average hospital charge for open heart surgery was 172% higher for patients with a length of stay greater than 18 days compared with 165% for patients less than 65 years of age. CONCLUSIONS: Higher operative mortality and longer length of stay in elderly patients, resulting in increased health care costs, was associated with more co-morbidities. These results suggest interventions designed to reduce congestive heart failure and other co-morbidities may improve patient's recovery and reduce costs.

Adult↗

Two new mutations of the glucose-6-phosphate dehydrogenase (G6PD) gene associated with haemolytic anaemia: clinical, biochemical and molecular relationships.

In two unrelated Spanish males with glucose-6-phosphate dehydrogenase (G6PD) deficiency and haemolytic anaemia, and two different novel point mutations in the G6PD gene, have been identified. A C to T transition at nucleotide 406 resulting in a (136) Arg to Cys substitution and a C to G transition at nucleotide 1155 resulting in a (385) Cys to Trp substitution. These two molecular defects have not been described before and are designated G6PD Valladolid 406 C-->T and G6PD Madrid 1155 C-->G. In vitro biochemical characterization of both mutant enzymes showed important differences in their molecular properties according to their different clinical behaviour. In G6PD Valladolid, the mutation of which is located in exon 5, the normal in vitro heat stability may explain its mild clinical expression (low-grade haemolysis interrupted by an acute haemolytic crisis at age 70). In G6PD Madrid, the mutation, located in exon 10, results in a deficient variant associated with neonatal jaundice and life-long chronic nonspherocytic haemolytic anaemia (CNSHA). This finding further emphasizes the importance of this specific region of the G6PD gene in the stabilization of the G6PD molecule. Putative relationships between these single point mutations and the molecular properties of the mutant enzymes are also discussed.

Anemia, Hemolytic↗

Protein kinase Sck1 is involved in trehalase activation by glucose and nitrogen source in the fission yeast Schizosaccharomyces pombe.

Trehalase activity is markedly enhanced upon addition of glucose and a nitrogen source to cells of the fission yeast Schizosaccharomyces pombe. This increase corresponds to a post-translational activation of the enzyme, which is controlled by cAMP-dependent and cAMP-independent pathways. Recent work has shown that overexpression of SCK1 in Schiz. pombe is able to suppress mutations that result in reduced Pka1 (cAMP-dependent protein kinase A activity, suggesting that Sck1 (suppressor of loss of cAMP-dependent protein kinase) might be a functional analogue of Pka1 in the fission yeast. Here, an analysis of the possible role of Sck1 in the activation of trehalase triggered by glucose and a nitrogen source is reported in cells that were deficient in either Pka1, Sck1 or both protein kinases. The results showed that, except in repressed cells, Sck1 probably mediates a cAMP-independent activation of trehalase following the signal(s) triggered by glucose and the nitrogen source. The absence of functional Sck1 in depressed cells renders trehalase insensitive to activation by glucose and the nitrogen source even in the presence of Pka1, indicating that the Sck1-dependent, cAMP-independent pathway is the main signalling pathway controlling trehalase activation under derepression conditions. It is proposed that, during the activation of trehalase induced by glucose or a nitrogen source, the cAMP-Pka1 activation pathway previously characterized is to some extent parallel to this newly described one which includes Sck1 as phosphorylating enzyme. Neither of these two pathways, however, plays a key role in the heat-induced increase in trehalase activity.

Enzyme Activation↗

Mercurialis annua: characterization of main allergens and cross-reactivity with other species.

A multicentric study was conducted to evaluate the frequency of Mercurialis annua pollen sensitization in several areas of Spain and to select a population sample to characterize the main allergenic components in M. annua pollen. Patients were recruited from six hospitals in Spain. Out of 420 patients sensitized to pollens, 195 (46.4%) showed positive skin tests to M. annua, thus evidencing the high level of sensitization to the pollen of this plant in Spain. Thirty-seven sera with RAST class values to M. annua > or = 3 were selected for SDS-PAGE immunoblotting analysis. Two main allergenic components with molecular weights of 15.8 and 14.1 kD were detected in 59 and 51% of the sera, respectively, and they were identified as profilins. Isolation of the relevant allergens was made by affinity chromatography on a poly-L-proline-Sepharose column, followed by gel filtration and anion exchange chromatography in the micropreparative SMARTs System. A significant but low antigenic cross-reactivity between M. annua and Olea europaea, Fraxinus elatior, Ricinus communis, Salsola kali, Parietaria judaica and Artemisia vulgaris was demonstrated by several in vitro techniques.

Adolescent↗

An analysis of the mechanisms involved in the okadaic acid-induced contraction of the estrogen-primed rat uterus.

The contractile effect of okadaic acid (OA) and its derivatives was investigated in the rat uterus. OA (20 microM) induced a transient contraction which, after plateauing, slowly decreased. The structurally related compound okadanol (20 microM) failed to induce any significant contraction. Conversely, the synthetic compound methyl okadaate (20 microM) and the naturally occurring ester 7'-hydroxy-4'-methyl-2'-methylen-hept-4'(E)-enyl okadaate (20 microM) were as active as the free acid. The OA-induced contraction was unaffected in the presence of neomycin (5 mM), mepacrine (30 microM), 1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperaz ine (10 microM), calphostin C (3 microM) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (30 microM). The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (100 microM) did not modify the amplitude of the OA-induced contraction but significantly increased the rate of tension decay. The myosin light chain kinase inhibitor 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (1 mM) significantly reduced the peak amplitude of the contraction. Staurosporine (0.03-0.1 microM) did not modify the contractile component of the OA-induced response but inhibited the subsequent decrease in tension. In freshly dispersed myometral cells loaded with the fluorescent Ca++ indicator indo 1, OA did not produce any significant increase in [Ca++]i. OA (5- to 90-min contact) also failed to modify the intracellular levels of arachidonic acid, compared with basal values. These data suggest that in the rat uterus 1) the contractile effect of OA (20 microM) is specifically mediated by inhibition of protein phosphatases type 1 and/or 2A and is related to a direct interaction with the contractile machinery; 2) the decreasing phase of the OA-induced mechanical response could be mediated by a staurosporine-sensitive protein kinase different from protein kinase C.

Animals↗

Allergic reactions to ampicillin. Studies on the specificity and selectivity in subjects with immediate reactions.

BACKGROUND: Ampicillin (AMP) is a drug that has been prescribed extensively. Reactions that have been reported include exanthema, desquamative contact eczema, urticaria and anaphylaxis. Experimental evidence indicates that the side chain of AMP is a structure that may induce a selective immune response either at the humoral or lymphocyte T-cell level. With regard to IgE reactions, the selectivity and specificity of the response needs to be studied in humans. OBJECTIVES: To study the specificity of the IgE response in a group of subjects who had an immediate allergic reaction after the administration of AMP. METHODS: Subjects developing an immediate response (anaphylaxis or urticaria) after the administration of AMP or an aminopenicillin derivative with the same side chain as AMP were studied. Skin tests were made to determinants generated from benzyl penicillin (BP): benzyl penicilloyl (BPO) and minor determinant mixture (MDM), as well as amoxicillin (AX) and AMP. Specific IgE antibodies were determined to benzyl penicilloyl polylisine (BPO-PLL), amoxicilloyl-polylisine (AX-PLL) and ampicilloyl-polylisine (AMP-PLL). The specificity of the IgE antibody response was studied by RAST and RAST inhibition. Subjects were classified in three categories: group A: those who were skin test and/or RAST positive to determinants derived from benzylpenicillin, group B: those who were negative to determinants derived from benzylpenicillin but were skin test and/or RAST positive to determinants derived from AX and AMP and group C: those who were exclusively positive to determinants derived from AMP. RESULTS: A total of 48 subjects was included in the study. In group A there were 35 cases, in group B 10 cases, and in group C three cases. RAST inhibition studies showed that in some instances the side chain of AMP could induce specific responses with a variable degree of crossreactivity between BP and AX. CONCLUSIONS: Although AMP can induce an immediate IgE response in subjects allergic to betalactams and the structure of the side chain may contribute to the specificity of the response, our results indicate that in most instances crossreactivity with the other penicillins exists and that in the groups studied selective reactions to just AMP derived determinants were uncommon.

Adult↗

Predictive value of prosthetic valve area index for early and late clinical results after valve replacement with the St Jude Medical valve prosthesis.

BACKGROUND: Previous studies indicate that a minimal prosthetic valve area index (VAI) of > or = 0.9 cm2/m2 for aortic and > or = 1.3 cm2/m2 for mitral valves minimizes postoperative pressure gradients. METHODS AND RESULTS: To determine VAI as an independent risk factor for postoperative events, 607 isolated aortic valve replacement (AVR) and 482 isolated mitral valve replacement (MVR) operations with the St Jude Medical valve were studied. End points included hospital deaths, NYHA functional class, late death and late valve-related death, major thromboembolism, anticoagulant-related hemorrhage, and reoperation. VAI was calculated from the ratio of prosthetic valve area to body surface area for each patient, and a range and mean were obtained for each valve size. Follow-up ranged from 1 to 120 months, totaled 2964 patient-years, and was 98% complete. Mean and range of VAI (cm2/m2) were 1.31 (0.74 to 2.86) in the aortic and 2.5 (1.4 to 6.32) in the mitral group. There were 33 AVR (5.4%) and 38 MVR (7.9%) hospital deaths. VAI was not a risk factor for NYHA class, early death, late death, or other postoperative events. The actuarial survival rates, 84% for AVR and 80% for MVR at 5 years, were not affected by VAI. CONCLUSIONS: Within the ranges measured, VAI did not influence the end points of the study.

Adolescent↗

Growth pattern and clinical correlation of subcutaneously inoculated human primary acute leukemias in severe combined immunodeficiency mice.

We examined the ability of patient-derived human leukemic blasts to generate leukemic growth and dissemination in severe combined immunodeficiency (SCID) mice by subcutaneous inoculation without conditioning treatment or administration of growth-promoting cytokines. Additionally, we correlated the growth pattern with the clinical outcome of patients from whom the leukemic cells were derived. The leukemias displayed three distinct growth patterns, ie, either aggressive, indolent, or no tumor growth. Leukemic cells from 6 of 13 patients with acute myeloid leukemia (AML), 4 of 7 T-cell acute lymphoblastic leukemia (T-ALL), and 11 of 16 patients with B-lineage ALL grew as subcutaneous tumors, with a significant number subsequently disseminating into distant organs in SCID mice. Patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SCID mice had a relatively poor clinical outcome, whereas patients with AML and T- or B-lineage ALL whose leukemic blasts grew indolently or whose cells failed to induce growth had a more favorable clinical course. Our study has shown that the subcutaneous inoculation of patient-derived human leukemic cells in SCID mice can engraft and grow as subcutaneous tumors with subsequent dissemination to distant organs in a manner analogous to their pattern of growth in humans. Additionally, these data suggest a clinical correlation to the growth and dissemination of some leukemic subtypes that may represent not only an additional prognosticator for patient outcome, but also a vehicle for the study of the biologic behavior of human leukemias and the development of novel therapeutic strategies.

Acute Disease↗

Neurite outgrowth through lesions of neonatal opossum spinal cord in culture.

The aim of these experiments was to analyze neurite outgrowth during regeneration of opossum spinal cord isolated from Monodelfis domestica and maintained in culture for 3-5 days. Lesions were made by crushing with forceps. In isolated spinal cords of animals aged 3 days, neurites entered the crush and grew along the basal lamina of the pia mater. Growth cones with pleiomorphic appearance containing vesicles, mitochondria and microtubules were abundant in the marginal zone, as were synaptoid contacts with active zones facing basal lamina. In preparations from animals aged 11-12 days, the lesion site was disrupted and contained only degenerating axons, debris and vesicles. Axons and growth cones entered the edge of the lesion but did not extend into it. Lesions in young animals extended over distances of more than 1 mm and contained no radial glia. The damaged area in older preparations was restricted to the crush site with normal astrocytes, oligodendrocytes and neurons immediately adjacent to the lesion. Thus, similar crushes produced more extensive damage in younger spinal cords that were capable of regeneration than in older cords that were not. Dorsal root ganglion fibers labeled with carbocyanine dye (DiI) were observed by video imaging as they grew through lesions. Individual growth cones examined subsequently by electron microscopy had grown again along pial basal lamina. After 5 days in culture dorsal root stimulation gave rise to discharges in ventral roots beyond the lesion indicating that synaptic connections were formed by growing fibers.

Animals↗

Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent.

An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.

Acute Disease↗

Peptide-mass profiles of polyvinylidene difluoride-bound proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in the presence of nonionic detergents.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), in conjunction with enzymatic digestion of proteins and molecular weight search of peptide-mass database is a powerful technique for peptide/protein identification. Ideally, peptide mixtures should be compatible with both MALDI-TOF and microsequencing. In our laboratory, enzymatic digestion and extraction of peptides from polyvinylidene difluoride (PVDF)-bound proteins is performed in the presence of nonionic detergents. However, nonionic detergents have been shown to cause signal suppression in MALDI-TOF analysis. This study demonstrates that by using a modified matrix solution, peptide-mass fingerprinting of PVDF-bound proteins by MALDI-TOF can be obtained in the presence of nonionic detergents such as hydrogenated Triton X-100 (RTX-100), octylglucopyranoside, and Tween 20.

Amino Acid Sequence↗

A survey for Cryptosporidium spp. in mammals at the Barcelona Zoo.

Mammals housed at the Barcelona Zoo belonging to the orders Carnivora, Artiodactyla, Perissodactyla and Proboscidea were examined for Cryptosporidium infections. A total of 183 fecal samples from 17 carnivores and 34 herbivores revealed patent infections in only 6 herbivore species (5 artiodactyls of the families Bovidae and Giraffidae and 1 perissodactyl of the family Rhinocerotidae); all carnivores were negative. Intensity of infection was found to be generally low. Connochaetes taurinus taurinus, Gazella dorcas neglecta, Kobus ellipsiprymmus and Giraffa camelopardalis constitute new host species for the parasite.

Animals↗

Esmolol and percutaneous cardiopulmonary bypass enhance myocardial salvage during ischemia in a dog model.

Despite recent advances in techniques of reperfusion for acute myocardial ischemia, myocardial salvage remains suboptimal. Beta-blockers have been shown to limit infarct size during acute ischemia, but their negative inotropic properties have limited their use. Cardiopulmonary bypass is an attractive technique for cardiac resuscitation because it can stabilize a hemodynamically compromised patient and potentially reduce myocardial oxygen consumption. In an attempt to maximize myocardial salvage in the setting of acute ischemia, the combination of esmolol, an ultrashort-acting beta-blocker, with percutaneous cardiopulmonary bypass was evaluated. Four groups of instrumented dogs underwent 2 hours of myocardial ischemia induced by occlusion of the proximal left anterior descending coronary artery, followed by 1 hour of reperfusion. Throughout the period of ischemia and reperfusion, esmolol plus percutaneous cardiopulmonary bypass was compared with esmolol alone, percutaneous cardiopulmonary bypass alone, and control conditions. After the reperfusion period, the extent of infarction of the left ventricle at risk was determined. Four animals had intractable arrhythmias: one in the esmolol plus bypass group, one in the esmolol group, and two in the control group. The extent of infarction of the left ventricle at risk was significantly reduced in the esmolol plus bypass group (30%) compared with bypass alone (52%), with esmolol alone (54%), and with the control groups (59%; p < 0.05). We conclude that in this experimental model the combination of esmolol with bypass improves myocardial salvage after ischemia and reperfusion.

Adrenergic beta-Antagonists↗

Selective allergic reaction to oral cloxacillin.

BACKGROUND: Previous observations indicate that in some instances subjects allergic to penicillins may experience an allergic reaction after taking the drug by one route but have good tolerance after being administered the same drug by a different route. OBJECTIVE: The purpose was to establish if cloxacillin (CLX) induced a selective response only after oral route administration in a suspected case and to study if there were differences between the oral and parenteral formulations. METHODS: Skin tests were carried out using benzylpenicillin (BP) conjugated to poly-L-lysine (BPO-PLL), minor determinant mixture of benzylpenicillin (MDM), ampicillin (AMP), amoxicillin (AX) and cloxacillin (CLX). Radioallergosorbent assay (RAST) was carried out using BPO-PLL, AX-PLL and CLX-PLL sensitized discs. In the case the skin tests and RAST were negative, a controlled challenge administering the drug by both oral and parenteral route was made. Urine samples were taken at prechallenge (basal levels) and at three periods after challenge (1-3, 3-6 and 6-9 h). Analysis of oral and parenteral formulations was made by HPLC chromatography. RESULTS: All skin tests and RASTs were negative. With the challenge tests the patient tolerated parenteral BP and oral phenoxymethyl penicillin (PV) and oral and parenteral AMP up to therapeutic concentrations. Parenteral CLX (500 mg) was also tolerated but 30 min after administering 50 mg by the oral route progressive generalized erythema with pruritus, facial angioedema and tachycardia developed. Urine samples taken during the challenge tests showed an increased excretion of N-methyl histamine (N-MH) 3 h after challenge with oral CLX but no change in N-MH levels after challenge with parenteral CLX or the other penicillins, indicating that histamine was released during the allergic episode with oral CLX. HPLC analysis of the oral and parenteral CLX formulations indicated that there were no differences and that neither polymers no other contaminant materials were present. CONCLUSION: Although the nature of the allergenic determinant involved in the induction of the reaction is not yet known, the oral route may have favoured the production of a metabolite not generated by the parenteral route.

Administration, Oral↗

Intestinal parasitism--protozoa and helminths--in primates at the Barcelona Zoo.

The faunistic results regarding intestinal parasitism by protozoa and helminths in 21 primate species (three Cebidae, thirteen Cercopithecidae, one Hylobatidae, one Lemuridae, three Pongidae) are reported. The primate species were housed in four separate galleries. Six faecal samples of each host species were subjected to coprological analysis. Fifteen parasite species were detected: 11 protozoa (Entamoeba coli, E. chattoni, E. hartmanni, Iodamoeba bütschlii, Endolimax nana, Giardia intestinalis, Chilomastix mesnilii, Enteromonas hominis, Trichomonas intestinalis, Balantidium coli, and Blastocystis hominis) and 4 helminths (Ancylostoma sp., Strongyloides fuelleborni, Strongyloides sp., and Trichuris trichiura). The results reveal certain parasitic similarities between host species housed in the same gallery; however, these primate species do not always carry identical parasite species.

Animals↗

Metastatic breast carcinoma presenting as obstructive jaundice.

A case of obstructive jaundice due to extrahepatic intraductal biliary metastasis from a breast carcinoma is reported. This clinical picture was a late manifestation and the first evidence of spread of the disease. The patient was treated by surgical decompression with relief of jaundice but died 5 months later. In patients with a history of carcinoma of the breast, the possibility of extrahepatic biliary metastasis should always be considered in the differential diagnosis of jaundice. Because this condition is amenable to palliation, it is important to differentiate it from jaundice due to hepatic involvement by this tumor.

Adenocarcinoma↗

Inhibition by polyols of the heat-shock-induced activation of trehalase in the yeast Zygosaccharomyces rouxii.

Trehalase activity was markedly enhanced in Zygosaccharomyces rouxii upon exposure of the cells to a heat shock. The increase in trehalase was independent of rapid changes in the intracellular concentration of cAMP and was not blocked by inhibitors of protein synthesis. Trehalase activated in vivo by heat shock was deactivated in vitro by phosphatase, suggesting that heat stress triggers a cAMP-independent signalling pathway that includes the activation of trehalase by phosphorylation of the enzyme protein. The addition to these cells before heating of either glycerol or other polyols produced a significant decrease in the heat-shock induced activation of trehalase. However, the trehalose content in cells heat-shocked in the presence of polyols did not increase significantly, indicating that these compounds may also influence the synthesis of the disaccharide.

Alkaline Phosphatase↗

The small aortic root and the Medtronic Hall valve: ultrafast computed tomography assessment of left ventricular mass following aortic valve replacement.

BACKGROUND AND AIMS OF THE STUDY: The selection of an appropriate size aortic valve substitute with respect to patient size and life-style, in the presence of a small aortic root, is problematic, and a decision to enlarge the aortic annulus is often arbitrary. An aortic valve substitute-patient mismatch may place an excessive load on the left ventricle resulting in residual left ventricular mass with attendant patient morbidity and mortality. The aim of this study was to assess the adequacy of the Medtronic Hall valve in the small aortic root using ultrafast computed tomography analysis of left ventricular mass. MATERIALS AND METHODS: In 13 patients the smallest Medtronic Hall valves (size 20 and 21; measured internal orifice area of 2.01 cm2 for both) were used to replace the native aortic valve. All patients had aortic stenosis, and left ventricular hypertrophy was established by echocardiography. The mean body surface area was 1.8 +/- 0.2 m2 (range 1.50-2.06 m2) and the mean weight was 75 +/- 15 Kg (range 50-97 Kg). The mean preoperative New York Heart Association functional class was 3.54 +/- 0.5. RESULTS: There was no operative or late mortality. At a mean follow up of 22 months after aortic valve replacement, the mean left ventricular mass index was 89 +/- 11.4 g/m2 (normal left ventricular mass index by ultrafast computed tomography = 97 +/- 14 g/m2) and mean New York Heart Association functional class was 1.6 +/- 0.8 (p (Binomial) = 0.0001 compared to preoperative). Doppler echocardiogram demonstrated a mean gradient across the prosthetic valve of 17 +/- 7 mmHg. There was no trend towards greater left ventricular mass index in patients with greater body surface area or weight. In no patient was the aortic annulus enlarged. CONCLUSIONS: Trends from this preliminary data suggest that implanting the smallest Medtronic-Hall aortic valves (sizes 20 and 21) results in normal left ventricular mass following aortic valve replacement in patients up to a body surface area of 2.06 m2 and provides support for the notion that an aortic annulus enlarging procedure was not necessary in this group of patients.

Adult↗