RESUMO
We report a case of visceral leishmaniasis and acute renal failure in a white male patient, 28 years of age, infected with the human immunodeficiency virus (HIV). The clinical presentation of the patient was diarrheic syndrome of long evolution, fever, hepatosplenomegaly and pancytopenia, accompanied by nephrotic syndrome and irreversible acute renal failure. Renal biopsy showed glomerular AA amyloid deposits. This is the first case described in humans of secondary amyloidosis caused by visceral leishmaniasis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Injúria Renal Aguda/etiologia , Amiloidose/etiologia , Leishmaniose Visceral/complicações , Adulto , Hepatite C Crônica/complicações , Dependência de Heroína/complicações , Humanos , Masculino , Proteína Amiloide A Sérica/análise , Abuso de Substâncias por Via Intravenosa/complicaçõesRESUMO
OBJECTIVE: To evaluate the level of compliance with the 2002 consensus document (Spanish Society of Nephrology) on guidelines for the detection, prevention and treatment of diabetic nephropathy in Catalonia. SUBJECTS AND METHODS: Multicenter (23 hospitals), observational, cross-sectional, descriptive study conducted in 413 diabetic patients (61.7% men, 38.3% women) with a median age of 66.2 +/-11.5 years (26-93 years). The ANOVA test (post-hoc analysis; p value< 0.05) was used to study the relationships between the stages of diabetic nephropathyand different variables. RESULTS: 90.3% of the patients had type 2 DM. The following anthropometric parameters were observed: BMI 29.8 +/- 5 kg/m2 (BMI > 30 kg/m2: 48.7%) and waist circumference 104.1 +/- 14 cm (48.6% men > 102 cm and 78.9% women > 88 cm). Serum creatinine 1.9 +/- 1.3 mg/dl and simplified MDRD equation 45.3 +/- 25.0 ml/min/1.73 m2 [65.8%with CKD stages 3 and 4]. 80% of patients had ophthalmologic examination and 52.8% antiplatelet treatment. Hb A1c was 7.3 +/- 1.3%, but the percentage of patients with glycated hemoglobin > 7% and 8% was 54.9 and 28.6% [only 50.2% had been seen by an endocrinologist in the last 6 months]. 52.8% of patients were treated with insulin and 44.1% with anti-diabetic drugs, although only 19.6% used the new anti-diabetic drugs. 61% of patients had an LDLc > 100 mg/dl (61% treated) and 44% had triglycerides (TG) > 150 mg/dl (72% treated). 95% of patients presented with hypertension (BP > or = 130/80 mmHg),91% were undergoing antihypertensive treatment (79.7% with angiotensin-converting enzyme inhibitors and / or angiotensin receptor blockers). 81% with microalbuminuria and 78%with established proteinuria were receiving anti-proteinuric treatment. Of the patients considered to be refractory to BP (>3 drugs), only 28.9% underwent ambulatory BP monitoring. Significant differences were observed between stages of diabetic nephropathy and glycated hemoglobin (HBA1c; p = 0.048), systolic blood pressure (SBP; p = 0.024), lipidic control (HDLc; p = 0.015 and TG; p = 0.034), anemia (Hb; p = 0.010) and CKD (creatinine and sMDRD; p = 0.000). The levels of compliance with the therapeutic objectives regarding lipid control (LDL < or = 100 mg/dl and TG< or = 150 mg/dl), BP < or = 130/80 mmHg and HbA1c < or =7% were 1 objective: 68%, 2 objectives: 21.8% and 3 objectives: only 4% of patients. CONCLUSIONS: According to the results of our study, only a reduced proportion of patients fulfilled the different therapeutic end-points indicated. Future measures will be directed at improving physician-patient relationships with the main aim of intensifying the therapeutic measures to attain better metabolic and blood pressure control, nephroprotection and prevention in the appearance of cardiovascular events.
Assuntos
Nefropatias Diabéticas/terapia , Fidelidade a Diretrizes/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/classificação , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Comorbidade , Creatinina/sangue , Estudos Transversais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/prevenção & controle , Feminino , Taxa de Filtração Glomerular , Hemoglobinas Glicadas/análise , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Abandono do Hábito de Fumar , Sociedades Médicas , Espanha/epidemiologia , Recusa do Paciente ao Tratamento/estatística & dados numéricosRESUMO
From 1989 to 1991, the level of resistance to ciprofloxacin in our hospital increased from 0.47% to 6.7% in opportunistic Enterobacteriaceae, from 9.9% to 16% in Pseudomonas aeruginosa and from 8.27% to 31.8% in Campylobacter jejuni-coli. We also observed an increase in quinolone consumption from 1.1 in 1989 to 1.5 defined daily doses per 1000 inhabitants per day in 1991.
Assuntos
Anti-Infecciosos/farmacologia , Ciprofloxacina/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Campylobacter/tratamento farmacológico , Resistência Microbiana a Medicamentos , Infecções por Enterobacteriaceae/tratamento farmacológico , Humanos , Infecções Oportunistas/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Espanha , Fatores de TempoRESUMO
The aim of this paper is to describe how interventions by clinical pharmacists can provide quality pharmaceutical care to inpatients. Evidence-based pharmacotherapy is necessary for the practice of clinical pharmacy. The use of published data, patient-specific data, and data generated by conducted research are discussed with respect to unit dose computer systems, nutrition teams, and pharmacokinetic services, based on the experience of an European hospital pharmacy. Incorporating evidence into clinical pharmacy activities results in added value to these services. The implementation of evidence-based pharmacotherapy is not an easy task for three reasons: a lack of scientific evidence in many medical areas, a lack of authority of pharmacists in Europe to take an active part in decision-making for drug prescribing, and reluctance of some physicians to accept pharmacists within the health care team. Also, efforts are required to change education programs at the universities in Europe to better prepare clinical pharmacists in pharmacotherapy and pharmaceutical care.
Assuntos
Medicina Baseada em Evidências , Pacientes Internados , Sistemas de Medicação , Serviço de Farmácia Hospitalar/normas , Atitude do Pessoal de Saúde , Árvores de Decisões , Educação em Farmácia/normas , Humanos , Distúrbios Nutricionais/prevenção & controle , Equipe de Assistência ao Paciente , Farmacêuticos , Serviço de Farmácia Hospitalar/economia , Risco , EspanhaRESUMO
Over a one year period we detected five cases of iatrogenic mineralocorticoidism secondary to topical application of creams containing 9-alpha-fluoro-prednisolone. Although the same product was involved in all cases, the clinical features differed and included two cases of myopathy and hypokalemic rhabdomyolysis, one of oedema and two of arterial hypertension. Discontinuation of treatment and administration of potassium supplements produced a rapid recovery and all patients remain well six months later.
Assuntos
Edema/induzido quimicamente , Fluprednisolona/efeitos adversos , Hipertensão/induzido quimicamente , Rabdomiólise/induzido quimicamente , Adolescente , Adulto , Idoso , Edema/sangue , Feminino , Humanos , Hipopotassemia/sangue , Hipopotassemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Rabdomiólise/sangueRESUMO
A microbiological quality control study of parenteral nutrition (PN) is presented. The study was carried out in the Pharmacy and Microbiology Services of the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) from April 1991 to May 1998 and represents more than 25,000 lipid-containing PN admixtures prepared during that 7-year period. A randomized sampling procedure according to the cumulative sum control charts was performed and a 0.45-microm membrane filtration method was used as the microbiological test. Validation showed that the method is sensitive for sterility tests. Bacterial growth was observed on 59 filters (4.58% of the samples). A second control was made for these positive outcomes, and bacterial growth was found in only two cases. The patients' clinical history was reviewed and no relation between the microorganisms of the nutrition and the results obtained from blood cultures was observed. The quality control study revealed a low incidence of contamination in our PN preparation process.
Assuntos
Bactérias/isolamento & purificação , Alimentos Formulados/normas , Técnicas Microbiológicas , Nutrição Parenteral/normas , Contaminação de Alimentos , Nutrição Parenteral/efeitos adversos , Nutrição Parenteral/métodos , Controle de Qualidade , Reprodutibilidade dos Testes , EspanhaRESUMO
The mass transfer area coefficient (MTC) is the best parameter for solute transport evaluation in continuous ambulatory peritoneal dialysis (CAPD) patients. We compared three simplified MTC methods (calculated according Garred, Krediet, or Lindholm) and the peritoneal equilibration test (PET) (Twardowski) to complex MTC (MTCX) (Randerson and Farrell) for urea and creatinine, by means of 29 tests performed in 24 stable CAPD patients. There were no significant differences (paired t-test) between MTCX and each of the simplified MTC, except for creatinine MTC calculated by Krediet's method, which was significantly different (MTCX: 9.36 +/- 4.32, K-MTC: 10.48 +/- 4.55, p < 0.05). Likewise, there was an acceptable correlation between complex MTC and each of the simplified methods including the PET. However, a more detailed study of the MTC's categorizations shows poor agreement with complex MTC categorization. Better results are obtained by PET categorization, which reaches good likelihood ratios either for positive or negative events. We conclude that simplified MTC or the dialysate/plasma ratio at 240 minutes for urea and creatinine has an acceptable correlation with complex MTC and can be useful in clinical practice. There is poor agreement between solute transport categorizations of simplified MTC and complex MTC. There is a better coincidence between the PET (D/P at 240 minutes) and complex MTC categorizations.
Assuntos
Diálise Peritoneal Ambulatorial Contínua , Peritônio/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Creatinina/metabolismo , Feminino , Humanos , Masculino , Matemática , Métodos , Pessoa de Meia-Idade , Ureia/metabolismoRESUMO
The authors report the case of a patient treated with amiodarone for syncopal ventricular tachycardia complicating idiopathic dilated cardiomyopathy in whom symptomatic hyperthyroidism led to a discussion of the different therapeutic options available in this type of case. Neomercazole treatment was prescribed with success enabling maintenance of the antiarrhythmic drug. The reputation of inefficacy of carbimazole should be reconsidered ; high dose therapy should probably be tried in patients with hyperthyroidism when withdrawal of the antiarrhythmic drug does not seem to be possible.
Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Antitireóideos/uso terapêutico , Carbimazol/uso terapêutico , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/tratamento farmacológico , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Esquema de Medicação , Seguimentos , Humanos , Hipertireoidismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Taquicardia Ventricular/tratamento farmacológico , Resultado do TratamentoRESUMO
The authors report the case of a very rare coronary malformation: atresia of the left main coronary artery. This anomaly was discovered in a marathon runner who presented effort angina with a positive exercise stress test. At coronary angiography, it was not possible to catheterise the left coronary artery and only a minuscle dimple could be visualised. Selective right coronary catheterisation showed a very large right coronary artery with retrograde injection of the whole of the left coronary network, as far as the left main stem. The authors did not suggest revascularisation because of the good functional tolerance of this malformation.
Assuntos
Angina Pectoris/etiologia , Anomalias dos Vasos Coronários/complicações , Corrida , Adulto , Angiografia Coronária , Anomalias dos Vasos Coronários/terapia , Eletrocardiografia , Teste de Esforço , Seguimentos , Humanos , Masculino , PrognósticoRESUMO
The authors report a case of myocarditis secondary to a Salmonella Virchow infection in a 20 year old non-immunodeficient man without a previous medical history. The outcome was favourable after treatment with fluoroquinolone. The features of this rare complication of non-typhic salmonella infection are discussed with respect to this and four other recently published cases.
Assuntos
Miocardite/microbiologia , Infecções por Salmonella/diagnóstico , Doença Aguda , Adulto , Humanos , Masculino , Miocardite/diagnóstico , Infecções por Salmonella/microbiologiaRESUMO
Permanent pacemaker electrode infection is rare but can be fatal. The authors report two cases presenting with spondylodiscitis, a previously described mode of presentation of valve endocarditis but not previously reported in this context. In one case, recurrent courses of antibiotics did not prevent repeated episodes of bacteraemia. In the second, the relapse of infection occurred at different sites of the vertebral column until surgical removal of the electrodes: the usual features of this pathology were observed: frequent but not constant infection at the site of the pacemaker implantation, making the diagnosis more difficult; delayed signs of spondylodiscitis after implantation of the pacemaker; recurrence of infection when antibiotic therapy alone was prescribed and, therefore, the need for surgical ablation of all implanted material. The authors underline the diagnostic value of transoesophageal echocardiography.
Assuntos
Discite/etiologia , Endocardite Bacteriana/etiologia , Marca-Passo Artificial/efeitos adversos , Infecções Estafilocócicas/etiologia , Idoso , Discite/microbiologia , Discite/terapia , Ecocardiografia , Eletrodos Implantados/efeitos adversos , Endocardite Bacteriana/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Infecções Estafilocócicas/terapiaRESUMO
The authors report the results of a single centre study of 50 consecutive patients (average age 66 +/- 14 years; 36 men), admitted between 1992 and 2001 to a peripheral hospital for infectious endocarditis (IE). The median interval to diagnosis was 57 days. There was an underlying cardiac disease in 52% of cases, usually valvular (42%). The site of the IE was the mitral valve in 21 cases, the aortic valve in 19 cases, mitro-aortic valves in 5 cases, native tricuspid valves in 2 cases and pacing catheters in 4 cases (associated with valvular endocarditis in one patient). The causal organism was usually a streptococcus (60%, including 28% of streptococcus bovis), or a staphylococcus (22%): no organism could be found in 7 patients. The average follow-up was 33 +/- 30 months: surgery was indicated in half the patients and 3 patients were turned down because of their poor general condition. In all, 34% of patients died (24% of their IE) in a median interval of 6 months, mainly from infectious or haemodynamic complications. Poor prognostic factors were: age > 70 years, "blind" antibiotic therapy, large-sized vegetations, embolism and renal failure. These data, comparable to the results observed in large series in the literature, underline the importance of multi-disciplinary management of IE and strict prophylaxis.
Assuntos
Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Idoso , Endocardite Bacteriana/complicações , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/cirurgia , França , Hemodinâmica , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Resultado do TratamentoRESUMO
The occurrence of a left atrial thrombus without a haemodynamic predisposing factor (arrhythmia, mitral valvulopathy, severe left ventricular dysfunction) is a rare event. We report a case during the progression of refractory myeloma, four months after stopping treatment with thalidomide. The promoting haemodynamic factors for left atrial thrombosis in sinus rhythm, described in the literature, had been excluded. In our case the potential role of thalidomide is debatable, in the light of recent publications about venous and arterial thromboses observed with this treatment.
Assuntos
Cardiopatias/induzido quimicamente , Mieloma Múltiplo/tratamento farmacológico , Talidomida/efeitos adversos , Trombose/induzido quimicamente , Idoso , Feminino , Átrios do Coração , HumanosRESUMO
Popliteal artery aneurysms are not so clinically frequent but are the most common site of peripheral aneurysms. They usually affect men aged over sixty and are caused by atherosclerosis. Whenever they concern younger men, other more unusual aetiologies such trauma, infection, inflammatory arteritis or popliteal entrapment are responsible. The authors report the first written observation of small size popliteal aneurysm, revealed by intermittent claudication in a 33 years old subject, of which the origin is accelerated atherosclerosis. The evolution after resection of the popliteal aneurysm and end-to-end anastomosis with saphenous vein was favorable. This observation reminds us of various popliteal aneurysm aetiologies, not excluding atherosclerosis due to young age and also underlines that the small size of these aneurysms does not protect against embolism risk.
Assuntos
Aneurisma/diagnóstico , Artéria Poplítea , Adulto , Anastomose Cirúrgica , Aneurisma/complicações , Aneurisma/cirurgia , Ecocardiografia Doppler , Humanos , Claudicação Intermitente/etiologia , Masculino , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Radiografia , Veia Safena/cirurgiaRESUMO
A 58-years-old man, with no medical past history, was examined for abdominal pain and weight loss. An enlarged kidney could be palpated, and abdominal echography showed left hydronephrosis due to ureteral compression by abdominal aortic aneurysm. Laboratory data showed an inflammatory syndrome. CT scan suggested the diagnosis of inflammatory abdominal aortic aneurysm. The use of corticosteroids brought about the regression of the symptoms and the resolution of the ureteral obstruction, permitting aneurysmectomy and prosthesis replacement without ureterolysis. This report shows the interest of preoperative radiological diagnosis of the inflammatory character of abdominal aneurysm. For uncomplicated cases, preoperative treatment using corticosteroids could allow partial regression of the periaortic inflammation and easier surgical repair.
Assuntos
Aneurisma da Aorta Abdominal/complicações , Aortite/complicações , Dor Abdominal/etiologia , Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/cirurgia , Aortite/diagnóstico por imagem , Aortite/tratamento farmacológico , Aortite/cirurgia , Implante de Prótese Vascular , Terapia Combinada , Fibrose , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esteroides , Tomografia Computadorizada por Raios X , Obstrução Ureteral/etiologiaRESUMO
A 78-year old man operated for an acute aortic dissection 8 years ago was hospitalized for an unusual clinical presentation with acute cor pulmonale and superior vena caval syndrome. He had poorly controlled high blood pressure, and coronary artery disease with aorto-coronary by-pass 10 years ago. He underwent Bentall procedure 2 years later for type I acute aortic dissection, with vein graft reimplantation on the valvular conduit. A pseudoaneurysm was noted in the post-operative period, which remained stable at 45 mm during the follow-up. Thoracic CT-scan highlighted a 14.5 cm diameter pseudoaneurysm compressing the superior vena cava and right pulmonary artery. Detached right aorto-coronary by-pass, suspected on transesophageal echocardiography, was confirmed peri-operatively; the aortic anastomosis blood in the peri-prosthetic space, explaining the acute clinical picture. The severity of the lesions did not permit surgical repair and the patient died during operation. This observation evidences the complications observed after aortic root replacement and favors echographic and radiological follow-ups (J Mal Vasc 1999; 24: 381-383).
Assuntos
Falso Aneurisma/complicações , Aorta/cirurgia , Ponte de Artéria Coronária , Complicações Pós-Operatórias , Falha de Prótese , Doença Cardiopulmonar/etiologia , Síndrome da Veia Cava Superior/etiologia , Doença Aguda , Idoso , Dissecção Aórtica/cirurgia , Falso Aneurisma/diagnóstico por imagem , Aorta/diagnóstico por imagem , Aneurisma Aórtico/cirurgia , Aortografia , Ecocardiografia Transesofagiana , Evolução Fatal , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Síndrome da Veia Cava Superior/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Hepatic tuberculosis is an exceptional form of presentation of extrapulmonary tuberculosis, but in the last years a greater incidence has been found in patients with HIV infection and/or consumptive diseases or immunosuppressive treatment. For this condition, the diagnosis of hepatic tuberculosis in other population groups represents a true clinical challenge because of the scarce specificity of both the clinical and biological manifestations. Despite deferral of the diagnosis, fast improvement is observed in the clinical symptomatology in most cases following initiation of tuberculostatic treatment.
Assuntos
Nefropatias Diabéticas/complicações , Tuberculose Hepática/complicações , Nefropatias Diabéticas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose Hepática/diagnósticoRESUMO
First cause of secondary hypertension is renovascular hypertension which presents abdominal bruit in 16 to 20% of cases. This clinical sign is also associated with other vascular disease of the abdomen such as celiac trunk stenosis and/or aneurysms located on the pancreaticoduodenal or gastroduodenal arcs level, with little representation among aneurysm. They usually appear on a context of digestive complications like neoplasias, chronic pancreatitis or gastric obstructions possibly with obstructive icterus, hemorrhage and acute abdomen episodes. Its presentation in other contexts is rare and constitutes a diagnostic challenge. Diagnosis is made by abdominal arteriography which is the best method because you can locate the problem as well as intervene therapeutically with embolization of the aneurysme. We would like to emphasize the importance of a quick diagnosis due to the risk of rupture and the high morbi-mortality associated.
Assuntos
Aneurisma/complicações , Arteriopatias Oclusivas/complicações , Auscultação , Artéria Celíaca/diagnóstico por imagem , Hipertensão Renovascular/diagnóstico , Aneurisma/diagnóstico por imagem , Aneurisma/terapia , Aneurisma Roto/prevenção & controle , Angioplastia , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/terapia , Artéria Celíaca/patologia , Artéria Celíaca/cirurgia , Constrição Patológica , Diagnóstico Precoce , Embolização Terapêutica , Feminino , Cefaleia/etiologia , Humanos , Hipertensão Renovascular/complicações , Hipertensão Renovascular/diagnóstico por imagem , Pessoa de Meia-Idade , Radiografia , SomRESUMO
Two cases of athero-embolic nephropathy unrelated with known precipitating factors such as aortic surgery, angiography, anticoagulation or pharmacological fibrinolysis are reported. In one, the histological study additionally disclosed endo-extracapillary proliferative glomerulonephritis. Hypocomplementemia or hypereosinophilia, which some authors consider very characteristic findings, could not be demonstrated in any of the two patients. The difficulties in the diagnosis of athero-embolic nephropathy and the possible indications of renal biopsy are discussed. Emphasis is made on prevention as the best approach to management, no specific treatment being available.
Assuntos
Arteriosclerose/complicações , Embolia/etiologia , Nefropatias/etiologia , Idoso , Biópsia , Colesterol , Diagnóstico Diferencial , Feminino , Humanos , Nefropatias/diagnóstico , Nefropatias/patologia , MasculinoRESUMO
The association of deep vein thrombosis with systemic necrotizing vasculitis is infrequent. Herein are referred two patients with microscopic polyarteritis and one patient with overlap syndrome who developed deep vein thrombosis which complicated in two cases with pulmonary embolism. The clinical features and the pathogenic mechanisms involved in this infrequent association are analyzed. In two patients the thrombosis was simultaneous with the diagnosis of vasculitis. In one patient deep vein thrombosis was the cause of hospital admission. Advanced age and thrombocytosis are factors associated to vasculitis, which may favor the development of thromboembolic disease. The presence of antiphospholipid syndrome was discarded. Although infrequent, this association should be considered because of the potential severe complications.