William Osler: Original Papers 1881-1897

Part 1: 1881-1888 On Some Points in the Etiology and Pathology of Ulcerative Endocarditis, 1881 On Certain Parasites in the Blood of the Frog, 1883 The Third Corpuscle of the Blood, 1883 On the Use of Arsenic in Certain Forms of Anaemia, 1886 Antifebrin, 1887 Case of Arterio-Venous Aneurism of the Axillary Artery and Vein of Fourteen Year's Duration, 1887 Typhilitis and Appendicitis, 1888 Part 2: 1889-1892 Annual Address - License to Practice 1889 Case of Syphiloma of the Cord of the Cauda Equina-Death From Diffuse Central Myelitis, 1889 On a Case of Simple Idiopathic Muscular Atrophy, Involving the Face and the Scapulo-Humeral Muscles, 1889 Note on Intra-Thoracic Growths Developing from the Thyroid Gland, 1889 On the Value of Laveran's Organisms in the Diagnosis of Malaria, 1889 On the Form of Convulsive Tic Associated with Corprolalia, Etc., 1890 A Case of Sensory Aphasia Word-blindness with Hemianopsia, 1891 Rudolf Virchow: The Man and the Student, 1891 The Healing of Tuberculosis, 1892 The Cold-Bath Treatment of Typhoid Fever, 1892 Part 3: 1893 Remarks on the Varieties of Chronic Chorea, and a Report Upon Two Families of the Hereditary Form, With One Autopsy, 1893 Note on Arsenical Neuritis Following the use of Fowler's Solution, 1893 Note on a Remarkable House Epidemic of Typhoid Fever, 1893 Cases of Sub-Phrenic Abscess, 1893 On Sporadic Cretinism in America, 1893 Notes on Tuberculosis in Children, 1893 Part 4: 1849-1895 Parotitis in Pneumonia, Case of Pericarditis Treated by Incision and Drainage, 1894 The Army Surgeon, 1894 Introductory Remarks to Course of Clinical Demonstrations on Typhoid Fever, 1894 Cancer of the Stomach with Very Rapid Course, 1895 Case of Sporadic Cretinism (Infantile Myxcedema) Treated Successfully with Thyroid Extract, 1895 Visible Contractile Tumour of the Pylorus Following Ulcer of the Stomach, 1895 On the Association of Enormous Heart Hypertrophy, Chronic Proliferative Peritonitis, and Recurring Ascites, with Adherent Pericardium, 1895 Teaching and Thinking the Two Functions of a Medical School, 1895 The Practical Value of Laveran's Discoveries, 1895 Part 5 1896 Addison's Disease, 1896 On Six Cases of Addison's Disease, 1896 Hemiplegia in Typhoid Fever Thomas Dover (of Dover's Powder) Physician and Buccaneer, 1896 John Keats The Apothecary Poet, 1896 On The Classification of the Tics or Habit Movements, 1896 The Cerebral Complication of Raynaud's Disease, 1896 Part 6: 1897 On Certain Features in the Prognosis of Pneumonia, 1897 Clinical Lecture on Mitral Stenosis - Sudden Death - Ball Thrombus in the Left Auricle, 1897 The Diagnosis of Malarial Fever, 1897 The Functions of a State Faculty (President's Address), 1897 A Clinical Lecture on The Ball-Valve Gall-Stone in the Common Duct, 1897 Pneumonia (Review of Cases studied), 1897 Internal Medicine as a Vocation, 1897 Back Notes

Expression of lipocalin-type prostaglandin D synthase (β-trace) in human heart and its accumulation in the coronary circulation of angina patients

Lipocalin-type prostaglandin D synthase (L-PGDS) is localized in the central nervous system and male genital organs of various mammals and is secreted as β-trace into the closed compartment of these tissues separated from the systemic circulation. In this study, we found that the mRNA for the human enzyme was expressed most intensely in the heart among various tissues examined. In human autopsy specimens, the enzyme was localized immunocytochemically in myocardial cells, atrial endocardial cells, and a synthetic phenotype of smooth muscle cells in the arteriosclerotic intima, and accumulated in the atherosclerotic plaque of coronary arteries with severe stenosis. In patients with stable angina (75–99% stenosis), the plasma level of L-PGDS was significantly (P < 0.05) higher in the great cardiac vein (0.694 ± 0.054 μg/ml, n = 7) than in the coronary artery (0.545 ± 0.034 μg/ml), as determined by a sandwich enzyme immunoassay. However, the veno-arterial difference in the plasma L-PGDS concentration was not observed in normal subjects without stenosis. After a percutaneous transluminal coronary angioplasty was performed to compress the stenotic atherosclerotic plaques, the L-PGDS concentration in the cardiac vein decreased significantly (P < 0.05) to 0.610 ± 0.051 μg/ml at 20 min and reached the arterial level within 1 h. These findings suggest that L-PGDS is present in both endocardium and myocardium of normal subjects and the stenotic site of patients with stable angina and is secreted into the coronary circulation.

Targeted deletion of all isoforms of the trkC gene suggests the use of alternate receptors by its ligand neurotrophin-3 in neuronal development and implicates trkC in normal cardiogenesis

We have generated null mutant mice that lack expression of all isoforms encoded by the trkC locus. These mice display a behavioral phenotype characterized by a loss of proprioceptive neurons. Neuronal counts of sensory ganglia in the trkC mutant mice reveal less severe losses than those in NT-3 null mutant mice, strongly suggesting that NT-3, in vivo, may signal through receptors other than trkC. Mice lacking either NT-3 or all trkC receptor isoforms die in the early postnatal period. Histological examination of trkC-deficient mice reveals severe cardiac defects such as atrial and ventricular septal defects, and valvular defects including pulmonic stenosis. Formation of these structures during development is dependent on cardiac neural crest function. The similarities in cardiac defects observed in the trkC and NT-3 null mutant mice indicate that the trkC receptor mediates most NT-3 effects on the cardiac neural crest.

An epidemiological needs assessment of carotid endarterectomy in an English health region. Is the need being met?

Objective: To compare the level of provision of carotid endarterectomy (an intervention of proved efficacy for prevention of stroke in patients with symptomatic high grade carotid artery stenosis) with estimates of need.

Regeneração hepática em animais jovens com estenose da veia porta ou ligadura da artéria hepática: estudos histológicos, moleculares e avaliação dos efeitos da insulina e do tacrolimus como agentes regenerativos

INTRODUÇÃO: O transplante hepático é o único tratamento efetivo para uma variedade de doenças hepáticas irreversíveis. No entanto, o número limitado de doadores pediátricos leva ao uso de enxertos hepáticos de doadores adultos, com necessidade de anastomoses vasculares mais complexas. Essas anastomoses tornam-se complicadas pela diferença no calibre dos vasos entre o doador e o receptor, resultando em alterações do fluxo sanguíneo, estenose da anastomose venosa ou arterial e trombose. Os efeitos para regeneração hepática decorrentes da privação do fluxo sanguíneo pela veia porta ou pela artéria hepática não estão completamente elucidados. Experimentalmente, quando um lobo do fígado não recebe o fluxo venoso portal, é observada atrofia deste segmento e hipertrofia do restante do órgão perfundido. Embora existam vários modelos experimentais para estudo da regeneração hepática, poucos são focados em animais em crescimento. Além disso, os efeitos regenerativos de drogas como o tacrolimus e a insulina precisam ser pesquisados, com o objetivo de encontrar um tratamento ideal para a insuficiência hepática ou um método de estimular a regeneração do fígado após ressecções ou transplantes parciais. O objetivo do presente estudo é descrever modelos de regeneração hepática em ratos em crescimento com: 1) ausência de fluxo hepático arterial e 2) redução do fluxo portal. Adicionalmente, o estudo avalia o efeito pró-regenerativo do tacrolimus e da insulina nesses modelos descritos. MÉTODOS: cento e vinte ratos (entre 50 e 100g de peso) foram divididos em 6 grupos, de acordo com o tipo de intervenção cirúrgica: Grupo 1, incisão abdominal sem intervenção hepática; Grupo 2, hepatectomia a 70%; Grupo 3, hepatectomia a 70% + estenose de veia porta; Grupo 4, hepatectomia a 70% + ligadura da artéria hepática; Grupo 5, hepatectomia a 70% + estenose de veia porta + insulina; Grupo 6, hepatectomia a 70% + estenose de veia porta + tacrolimus. Os animais dos grupos 1 ao 4 foram subdivididos em 5 subgrupos de acordo com o momento da morte: 1, 2, 3, 5 e 10 dias após a intervenção cirúrgica. Os animais dos grupos 5 e 6 foram subdividos em 2 subgrupos de acordo com o momento da morte: 2 e 10 dias após a intervenção cirúrgica. Os lobos hepáticos remanescentes foram submetidos à análise histomorfométrica, imuno-histoquímica e molecular. RESULTADOS: Verificou-se que no grupo com hepatectomia a 70% houve recuperação do peso do fígado no terceiro dia com aumento da atividade mitótica, enquanto que no grupo com estenose portal não se observou esse fenômeno (p < 0,001). A insulina e o tacrolimus promoveram aumento do peso do fígado e do índice mitótico. A atividade mitótica foi considerada aumentada nos animais dos grupos hepatectomia, hepatectomia + ligadura da artéria, insulina e tacrolimus; e esse parâmetro estava reduzido no grupo submetido à hepatectomia + estenose portal (p < 0,001). A expressão de interleucina 6 estava presente em todos os animais, sendo significativamente maior nos grupos hepatectomia, hepatectomia + ligadura da artéria e significativamente menor no grupo hepatectomia + estenose portal. Entretanto, a administração de tacrolimus ou insulina recuperou os níveis teciduais de interleucina 6 no grupo com estenose portal. CONCLUSÕES: No presente estudo foi padronizado um modelo simples e facilmente reprodutível para estudar a regeneração hepática em ratos em crescimento com redução do fluxo arterial ou venoso para o fígado. Foi demonstrado que a administração de insulina ou tacrolimus é capaz de reverter os efeitos deletérios da estenose portal na regeneração hepática. A obstrução do fluxo arterial não afetou a capacidade regenerativa hepática

Functional outcomes after stabilization with Dynesys in patients with spinal degenerative diseases

Objective: To know the impact of the Dynesys system on the functional outcomes in patients with spinal degenerative diseases. Summary of background data: Dynesys system has been proposed as an alternative to vertebral fusion for several spinal degenerative diseases. The fact that it has been used in people with different diagnosis criteria using different tools to measure clinical outcomes makes very difficult unifying the results available nowadays. Methods: The data base of Medlars Online International Literature (MEDLINE) via PubMed©, EMBASE©, and the Cochrane Library Plus were reviewed in search of all the studies published until November 2012 in which an operation with Dynesys in patients with spinal degenerative diseases and an evaluation of the results by an analysis of functional outcomes had taken place. No limits were used to article type, date of publication or language. Results: A total of 134 articles were found, 26 of which fulfilled the inclusion criteria after being assessed by two reviewers. All of them were case series, except for a multicenter randomized clinical trial (RCT) and a prospective case-control study. The selected articles made a total of 1507 cases. The most frequent diagnosis were lumbar spinal canal stenosis (LSCS), degenerative disc disease (DDD), degenerative spondylolisthesis (DS) and lumbar degenerative scoliosis (LDS). In cases of lumbar spinal canal stenosis Dynesys was associated to surgical decompression. Several tools to measure the functional disability and general health status were found. Oswestry Disability Index (ODI), the ODI Korean version (K-Odi), Prolo, Sf-36, Sf-12, Roland-Morris disability questionnaire (RMDQ), and the pain Visual Analogue Scale (VAS) were the most used. They showed positive results in all cases series reviewed. In most studies the ODI decreased about 25% (e.g. from a score of 85% to 60%). Better results when dynamic fusion was combined with nerve root decompression were found. Functional outcomes and leg pain scores with Dynesys were statistically non-inferior to posterolateral spinal fusion using autogenous bone. When Dynesys and decompression was compared with posterior interbody lumbar fixation (PLIF) and decompression, differences in ODI and VAS were not statistically significant. Conclusions: In patients with spinal degenerative diseases due to degenerative disc disorders, spinal canal stenosis and degenerative spondylolisthesis, surgery with Dynesys and decompression improves functional outcomes, decreases disability, and reduces back and leg pain. More studies are needed to conclude that dynamic stabilization is better than posterolateral and posterior interbody lumbar fusion. Studies comparing Dynesys with decompression against decompression alone should be done in order to isolate the effect of the dynamic stabilization.

Renovascular hypertension in a 12 month old boy: what can the radiologist do?

We report a clinical case of renovascular disease, probably linked to fibromuscular dysplasia, in a 12 months old boy with severe arterial hypertension with target-organ damage, highlighting the radiological approach. Initial investigation included renal ultrasound that showed normal sized kidneys, with normal cortical echogenicity on the right and focally increased echogenicity of the posterior aspect of the left kidney, forming a mass-like lesion. Magnetic resonance imaging excluded renal tumor, which was confirmed by ultrasound guided biopsy. A doppler ultrasonography was also performed suggesting a right renal artery stenosis and decreased flow to the posterior aspect of the left kidney. Angiography with diagnostic and therapeutic intention was performed: right renal artery stenosis was detected and transluminal ballon dilation was performed; the left renal artery bifurcated precociously and the branch that irrigated the posterior part of the kidney had a stenosis which was also successfully dilated. After the intervention good blood pressure control with antihypertensive drugs was achieved, which was not possible before the angiographic procedure. The authors underline various methods of imaging used to accurately diagnose renovascular disease and the usefulness of interventional radiology treatment for this disease in very young children.

Inflamação na aterosclerose : impacto na doença coronária

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Vitamin D in patients with atherosclerosis : a link between atherosclerosis and bone mass ?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Réduction des artéfacts de tuteur coronarien au moyen d’un algorithme de reconstruction avec renforcement des bords : étude prospective transversale en tomodensitométrie 256 coupes

Les artéfacts métalliques entraînent un épaississement artéfactuel de la paroi des tuteurs en tomodensitométrie (TDM) avec réduction apparente de leur lumière. Cette étude transversale prospective, devis mesures répétées et observateurs avec méthode en aveugle, chez 24 patients consécutifs/71 tuteurs coronariens a pour objectif de comparer l’épaisseur de paroi des tuteurs en TDM après reconstruction par un algorithme avec renforcement des bords et un algorithme standard. Une angiographie coronarienne par TDM 256 coupes a été réalisée, avec reconstruction par algorithmes avec renforcement des bords et standard. L’épaisseur de paroi des tuteurs était mesurée par méthodes orthogonale (diamètres) et circonférentielle (circonférences). La qualité d’image des tuteurs était évaluée par échelle ordinale, et les données analysées par modèles linéaire mixte et régression logistique des cotes proportionnelles. L’épaisseur de paroi des tuteurs était inférieure avec l’algorithme avec renforcement des bords comparé à l’algorithme standard, avec les méthodes orthogonale (0,97±0,02 vs 1,09±0,03 mm, respectivement; p<0,001) et circonférentielle (1,13±0,02 vs 1,21±0,02 mm, respectivement; p<0,001). Le premier causait moins de surestimation par rapport à l’épaisseur nominale comparé au second, avec méthodes orthogonale (0,89±0,19 vs 1,00±0,26 mm, respectivement; p<0,001) et circonférentielle (1,06±0,26 vs 1,13±0,31 mm, respectivement; p=0,005) et diminuait de 6 % la surestimation. Les scores de qualité étaient meilleurs avec l’algorithme avec renforcement des bords (OR 3,71; IC 95% 2,33–5,92; p<0,001). En conclusion, la reconstruction des images avec l’algorithme avec renforcement des bords génère des parois de tuteurs plus minces, moins de surestimation, et de meilleurs scores de qualité d’image que l’algorithme standard.

Long-Term Clinical and Imaging Follow-Up After Reinforced Pulmonary Autograft Ross Procedure.

The Ross operation remains a controversially discussed procedure when performed in the full root technique because concern exists regarding late dilatation of the pulmonary autograft and regurgitation of the neo-aortic valve. In 2008, we published our short-term experience when using external reinforcement of the autograft, which was inserted into a prosthetic Dacron graft. This detail was thought to prevent neoaortic root dilatation. Since 2006, 22 adult patients have undergone a Ross procedure using this technique. Indications were aortic regurgitation (n = 2), aortic stenosis (n = 15), and combined aortic stenosis and insufficiency (n = 5). A bicuspid aortic valve was present in 10 patients. Prior balloon valvuloplasty had been performed in seven patients. No early or late deaths occurred in this small series. One patient required aortic valve replacement early postoperatively, but freedom from late reoperation is 100% in the 21 remaining patients. Echocardiography confirmed the absence of more than trivial aortic insufficiency in 15 patients after a mean of 70 months (range, 14 to 108 months). No autograft dilatation was observed during follow-up and all patients are in New York Heart Association Class I. Autograft reinforcement is a simple and reproducible technical adjunct that may be especially useful in situations known for late autograft dilatation, namely, bicuspid aortic valve, predominant aortic insufficiency, and ascending aortic enlargement. The mid- to long-term results are encouraging because no late aortic root enlargement has been observed and the autograft valve is well functioning in all cases.

The sutureless aortic valve at 1 year: A large multicenter cohort study

OBJECTIVE Sutureless aortic valve replacement (AVR) offers an alternative to standard AVR in aortic stenosis. This prospective, single-arm study aimed to demonstrate safety and effectiveness of a bovine pericardial sutureless aortic valve at 1 year. METHODS From February 2010 to September 2013, 658 patients (mean age 78.3 ± 5.6 years; 40.0% octogenarian; 64.4% female; mean Society of Thoracic Surgeons score 7.2 ± 7.4) underwent sutureless AVR in 25 European centers. Concomitant cardiac procedures were performed in 29.5% and minimally invasive cardiac surgery in 33.3%. RESULTS One-year site-reported event rates were 8.1% for all-cause mortality, 4.5% for cardiac mortality, 3.0% for stroke, 1.9% for valve-related reoperation, 1.4% for endocarditis, and 0.6% for major paravalvular leak. No valve thrombosis, migration, or structural valve deterioration occurred. New York Heart Association class improved at least 1 level in 77.5% and remained stable (70.4% New York Heart Association class I or II at 1 year). Mean effective orifice area was 1.5 ± 0.4 cm(2); pressure gradient was 9.2 ± 5.0 mm Hg. Left ventricular mass decreased from 138.5 g/m(2) before surgery to 115.3 g/m(2) at 1 year (P < .001). Echocardiographic core laboratory findings confirmed that paravalvular leak was rare and remained stable during follow-up. CONCLUSIONS The Perceval sutureless valve resulted in low 1-year event rates in intermediate-risk patients undergoing AVR. New York Heart Association class improved in more than three-quarters of patients and remained stable. These data support the safety and efficacy to 1 year of the Perceval sutureless valve in this intermediate-risk population.

Posterior circulation cerebrovascular syndromes: diagnosis and management.

One in five strokes affects the posterior circulation. Diagnosing posterior circulation stroke can be challenging, as the vascular anatomy can be variable, and because presenting symptoms are often non-specific and fluctuating. Nevertheless, making the correct diagnosis is important, as these strokes have a high chance of recurrence, can be life threatening, and can lead to equally life-threatening complications. Investigation and management largely follow those for stroke in general, although some specific differences exist. These include the preferred use of MRI for diagnosing posterior fossa lesions, the management of basilar artery thrombosis, which may have a longer time window for recanalisation therapy, and the use of endovascular therapies for secondary prevention, which, so far, have not shown any benefit in the treatment of vertebral or basilar artery stenosis. In this review, we summarise the anatomy, aetiology and presentation of posterior circulation stroke, and discuss current approaches to management.

Outpatient management of abnormal smears

Objectives: To review the results of the first 403 women treated at the Abnormal Smear and Colposcopy Unit with special reference to the utility, efficacy, acceptability and economy of in-office treatment of cervical lesions by large loop or Fischer cone excision. Design: Retrospective chart review of consecutive patients treated following, referral with an abnormal smear or abnormal cervical morphology, between 1 September 1996 and I August 2001. Setting: Inner city private practice. Sample: A total of 403 consecutive General Practitioner referred women. Methods: Details of referral smear result, colposcopically directed biopsy result, subsequent treatment type and histological result including assessability number of specimens submitted, complications and follow-up assessment were extracted at chart review. Costs of public hospital inpatient and outpatient care, supplied by the Casemix and Clinical Benchmarking Service, Mater Miseraecordae Public Hospitals (with permission to publish), were compared with Medicare rebates. Main outcome measures: A total of 187 women were treated by large loop excision of the transformation zone, and 216 by Fischer cone excision. The number of women who were treated as outpatients under local anaesthetic were 395, while eight patients were treated under general anaesthesia as inpatients. There was poor correlation between referring smear, biopsy and subsequent treatment results. Eight patients had abnormal cytology at follow-up, of whom two have been retreated. Three patients had primary or secondary bleeding requiring treatment and two developed cervical stenosis. Outpatient private practice treatment of women with abnormal smears allows significant savings to the public purse over public or private hospital care. Conclusions: Outpatient treatment of women with abnormal smears, using the Fischer cone technique, is safe, wen accepted, effective and the most cost efficient solution to this public health problem.

Incremental benefit of myocardial contrast to combined dipyridamole-exercise stress echocardiography for the assessment of coronary artery disease

Background-Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD). Methods and Results-MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity. Conclusions-The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent.