Mucins are jelly-like acid glycosaminoglycans (formerly known as mucopolysaccharides) of the ground substances and probably play a part in the extravascular exchange of metabolites. Mucin is normally produced in small quantities by fibroblasts. Acid glycosaminoglycans, such as hyaluronic acid and heparin, stain with toluidine blue, colloidal iron, or with alcian blue at pH 2.5, the coloration depending on the number and nature of the acid groups. PAS stains heparin, but not hyaluronic acid. In general, acid glycosaminoglycans stain much brighter in frozen fixed tissue, or in 1% cetylpyridinium chloride solution, rather than in formalin-fixed biopsies.
Classification of the cutaneous mucinoses:
1- Primary
2- Secondary
Dermoscopy or epiluminescence microscopy
A simple, noninvasive method to examine the subsurface features of the skin.
Structures seen
Epidermis
Dermoepidermal junction
Superficial dermis
3 types of dermoscope
1.Nonpolarized devices
2.Polarized devices
3.Hybrid devices
Dermoscopy is used in:
1.Evaluating pigmented skin lesions
2.Evaluating nonpigment skin lesions
3.Entomodermoscopy
4.Trichoscopy
5.Onychoscopy
different dermoscopic patterns are used to diagnose the dermatological diseases are
1. melanocytic patterns:
Pigmentary patterns: typical pigment pattern, atypical pigment patter, pseudonetwork
dots and globules
Blue white veil
star brust pattern
2, Non melanocytic pattern:
milia like cyst
comedo like opening
3. vascular patterns:
lacunae
arborizing vessels
comma like vessels
corkscrew vessel
red dots
glomerular vessels
linear vessels
etc
Mucins are jelly-like acid glycosaminoglycans (formerly known as mucopolysaccharides) of the ground substances and probably play a part in the extravascular exchange of metabolites. Mucin is normally produced in small quantities by fibroblasts. Acid glycosaminoglycans, such as hyaluronic acid and heparin, stain with toluidine blue, colloidal iron, or with alcian blue at pH 2.5, the coloration depending on the number and nature of the acid groups. PAS stains heparin, but not hyaluronic acid. In general, acid glycosaminoglycans stain much brighter in frozen fixed tissue, or in 1% cetylpyridinium chloride solution, rather than in formalin-fixed biopsies.
Classification of the cutaneous mucinoses:
1- Primary
2- Secondary
Dermoscopy or epiluminescence microscopy
A simple, noninvasive method to examine the subsurface features of the skin.
Structures seen
Epidermis
Dermoepidermal junction
Superficial dermis
3 types of dermoscope
1.Nonpolarized devices
2.Polarized devices
3.Hybrid devices
Dermoscopy is used in:
1.Evaluating pigmented skin lesions
2.Evaluating nonpigment skin lesions
3.Entomodermoscopy
4.Trichoscopy
5.Onychoscopy
different dermoscopic patterns are used to diagnose the dermatological diseases are
1. melanocytic patterns:
Pigmentary patterns: typical pigment pattern, atypical pigment patter, pseudonetwork
dots and globules
Blue white veil
star brust pattern
2, Non melanocytic pattern:
milia like cyst
comedo like opening
3. vascular patterns:
lacunae
arborizing vessels
comma like vessels
corkscrew vessel
red dots
glomerular vessels
linear vessels
etc
Made as a part of residency programme of MD Dermatology Venerology and leprology. includes diabetes, thyroid disorders, pituitary disorders, metabolic syndrome,
Lichenoid Dermatoses, Characteristics of Lichenoid Dermatoses, What are the Major Lichenoid Dermatoses, Lichen planus (LP), Introduction of LP, Epidemiology of LP, Etiology of LP, Pathogenesis of LP, Clinical Features & Clinical variants of LP, Histopathology of LP, Immunohistochemistry of LP, Differential Diagnosis of LP, Treatment of LP
Slides prepared and compiled by highly experienced ENT teacher, Dr. Krishna Koirala from Nepal , for teaching undergraduate and postgraduate ENT students in the field of otorhinolaryngology.
A clear and concise explanation of the basic concepts in the subject matter concerned.
He is the Head of department with a sound knowledge in the field of ENT to teach both undergraduate and postgraduate ENT students
Made as a part of residency programme of MD Dermatology Venerology and leprology. includes diabetes, thyroid disorders, pituitary disorders, metabolic syndrome,
Lichenoid Dermatoses, Characteristics of Lichenoid Dermatoses, What are the Major Lichenoid Dermatoses, Lichen planus (LP), Introduction of LP, Epidemiology of LP, Etiology of LP, Pathogenesis of LP, Clinical Features & Clinical variants of LP, Histopathology of LP, Immunohistochemistry of LP, Differential Diagnosis of LP, Treatment of LP
Slides prepared and compiled by highly experienced ENT teacher, Dr. Krishna Koirala from Nepal , for teaching undergraduate and postgraduate ENT students in the field of otorhinolaryngology.
A clear and concise explanation of the basic concepts in the subject matter concerned.
He is the Head of department with a sound knowledge in the field of ENT to teach both undergraduate and postgraduate ENT students
STI information with content knowledge of what is important relating to protecting oneself. This is targeted for 16yer old students as teaching support and may contain some graphic pictures.
NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCEBad Blo.docxvannagoforth
NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE
“Bad Blood” by Fourtner, Fourtner, & Herreid Page 1
by
A.W. Fourtner, C.R. Fourtner and C.F. Herreid
University at Buff alo, State University of New York
Bad Blood:
A Case Study of the Tuskegee Syphilis Project
The Disease
Syphilis is a venereal disease spread during sexual intercourse. It can
also be passed from mother to child during pregnancy. It is caused
by a corkscrew-shaped bacterium called a spirochete, Treponema
pallidum. Th is microscopic organism resides in many organs of
the body but causes sores or ulcers (called chancres) to appear
on the skin of the penis, vagina, mouth, and occasionally in the
rectum, or on the tongue, lips, or breast. During sex the bacteria
leave the sores of one person and enter the moist membranes of
their partner’s penis, vagina, mouth, or rectum.
Once the spirochetes wiggle inside a victim, they begin to multiple
at an amazing rate. (Some bacteria have a doubling rate of 30
minutes. You may want to consider how many bacteria you might
have in 12 hours if one bacterium entered your body doubling
at that rate.) Th e spirochetes then enter the lymph circulation,
which carries them to nearby lymph glands that may swell in
response to the infection.
Th is fi rst stage of the disease (called primary syphilis) lasts only a
few weeks and usually causes hard red sores or ulcers to develop
on the genitals of the victim, who can then pass the disease on
to someone else. During this primary stage, a blood test will not
reveal the disease but the bacteria can be scraped from the sores.
Th e sores soon heal and some people may recover entirely without
treatment.
Secondary syphilis develops two to six weeks after the sores heal. Th en fl u-like symptoms appear with fever,
headache, eye infl ammation, malaise, and joint pain, along with a skin rash and mouth and genital sores.
Th ese symptoms are a clear sign that the spirochetes have traveled throughout the body by way of the lymph
and blood systems, where they now can be readily detected by a blood test (e.g., the Wassermann test). Scalp
hair may drop out to give a “moth-eaten” look to the head. Th is secondary stage ends in a few weeks as the
sores heal.
Signs of the disease may never reappear even though the bacteria continue to live in the person. However, in
about 25% of those originally infected, symptoms will fl are up again in a late or tertiary stage syphilis.
NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE
“Bad Blood” by Fourtner, Fourtner, & Herreid Page 2
Almost any organ can be attacked, such as the cardiovascular system, producing leaking heart valves and
aneurysms—balloon-like bulges in the aorta that may burst, leading to instant death. Gummy or rubbery
tumors fi lled with spirochetes and covered by a dried crust of pus may develop on the skin. Th e bones may
deteriorate as in osteomyelitis or tuberculosis and may produce disfi guring facial mutilations as na ...
padmashree school of public health
Cohort studies are a type of longitudinal study—an approach that follows research participants over a period of time (often many years). Specifically, cohort studies recruit and follow participants who share a common characteristic, such as a particular occupation or demographic similarity.
Clinical microbiology and molecular techniquesIndhra Yogaesh
Molecular biology is the science of biomolecules. Even though the term “biomolecules” includes all molecules such as proteins, fatty acids etc, it is refers to nucleic acid these days.
The application of molecular technology in medicine is almost endless, some of the applications of molecular methods are:
1. Classification of organism based on genetic relatedness (genotyping)
2. Identification and confirmation of isolate obtained from culture
3. Early detection of pathogens in clinical specimen
4. Rapid detection of antibiotic resistance
5. Detection of mutations
6. Differentiation of toxigenic from non-toxigenic strains
7. Detection of microorganisms that lose viability during transport, impossible, dangerous and costly
to culture, grow slowly or present in extremely small numbers in clinical specimen
8. Apart from their role in microbiology, these techniques can also be used in identifying
abnormalities in human and forensic medicine.
Tracing the History of HIV: Exploring Controversial PointsSunidhi Singh
Take a deep dive into the intricate history of HIV as we navigate through its origins, epidemiological milestones, and contentious debates. Uncover controversial points such as the origins of the virus, early responses to the epidemic, controversies surrounding HIV/AIDS denialism, and the development of antiretroviral therapies. This presentation offers a nuanced perspective on the multifaceted journey of HIV/AIDS, highlighting key controversies that have shaped our understanding and response to this global health crisis.
Epidemiology & Control measures for Tuberculosis. AB Rajar
n this Lecture I tried my best to include all essential features about the TB disease. I hope that this will help to undergraduate Medical students for better understanding the Disease.
Katherine Promer Flores, MD (she/her)
Staff Physician
Division of Infectious Diseases and Global Public Health
Department of Medicine
University of California San Diego
Daniel Lee, MD
Clinical Professor of Medicine
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Leandro Mena, MD, MPH
Chair and Professor of Population Health Science
Department of Population Health Science
University of Mississippi Medical Center
Maile Young Karris, MD
Associate Professor
Co-Director San Diego Center for AIDS Research Clinical Investigations Core
Divisions of Infectious Diseases & Global Public Health and Geriatrics & Gerontology
Department of Medicine
University of California San Diego
Edward Cachay, MD, MAS
Professor of Medicine
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Gabriel Wagner, MD
Associate Clinical Professor
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Jocelyn Keehner, MD
Infectious Disease Fellow
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Richard Garfein, PhD, MPH
Professor
Herbert Wertheim School of Public Health and Human Longevity Science
Adjunct Professor
Division of Infectious Disease and Global Public Health
Department of Medicine
University of California, San Diego
Laura Bamford, MD, MSCE
Associate Professor of Medicine
Medical Director, Owen Clinic
Division of Infectious Diseases and Global Public Health
Department of Medicine
University of California, San Diego
Davey Smith, MD, MAS
Professor of Medicine
Chief, Division of Infectious Diseases and Global Public Health
Co-Director, San Diego Center for AIDS Research (CFAR)
Department of Medicine
University of California, San Diego
Elliot Welford, MD
Infectious Diseases Fellow
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Darcy Wooten, MD
Assistant Professor of Medicine
Associate Program Director, Infectious Diseases Fellowship
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Amutha Rajagopal, MD
Associate Physician Diplomate
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
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Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
The Great Imitator in 2013 – Syphilis and HIV Infection
1. The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease clinicians, physicians and
researchers. The goal of these presentations is to provide the most
current research, clinical practices and trends in HIV, HBV, HCV, TB
and other infectious diseases of global significance.
The slides from the AIDS Clinical Rounds presentation that you are
about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.
AIDS CLINICAL ROUNDS
2. History
• 56 y.o Caucasian gay man with longstanding HIV
infection presents with fever and rash
• HIV diagnosed in 1986 – initially not in care
• Presented with PCP in 1994; Nadir CD4 count <10
cells/mm3
• Initiated antiretroviral therapy and did well with
CD4 count 382 cells/mm3 (18%) by Feb 2011
• HIV RNA (viral load) <48 copies/mL (undetectable)
• In autumn 2011 noted onset of fatigue, malaise
• Noted to have mildly elevated AST, ALT (new)
3. Biopsy results
• Liver biopsy 2/29/2012
– MILD TO MODERATELY ACTIVE INTERFACE AND LOBULAR
HEPATITIS WITH PLASMA CELLS AND MILD PERIPORTAL
CHOLESTASIS. PERIPORTAL AND PORTAL-PORTAL BRIDGING
FIBROSIS ARE SEEN IN ASSOCIATION WITH THE
INFLAMMATION
– SUSPICIOUS FOR AUTOIMMUNE HEPATITIS
4. Treatment
• Treatment for autoimmune hepatitis :
– Prednisone at 60mg started on 5 March 2012
– Azathioprine 150mg daily added on 13 March
• Approximately 48 hours after starting
azathioprine, rash developed
– Mainly on extremities
– Non-tender, non-pruritic
• Subsequently noted fever to 101.6 F
• Worsening malaise and fatigue
6. Physical Examination
• T 38.9 C BP 112/52 HR 96 RR 16
• O2 sat 97% on 2L
• Alert and oriented, well-appearing
• Exam unremarkable except for rash
– Pale macular rash primarily involving palms, soles
– Extends to thighs and distal arms
– Spares trunk
7.
8.
9. Laboratory studies
• CBC:
– WBC 10.9 (72% N, 1% eos), Hgb 12.9, Plt 317
• Chemistries: Na 127, K 4.5, Cr 1.2
• ALT 55, AST 40, Alk phos 198, Alb 3.3
• U/A unremarkable
• CXR: no acute abnormalities
RPR reactive 1:256 – T. pallidum EIA positive
10. Update
• Liver biopsy 2/29
– MILD TO MODERATELY ACTIVE INTERFACE AND LOBULAR HEPATITIS WITH
PLASMA CELLS AND MILD PERIPORTAL CHOLESTASIS. PERIPORTAL AND
PORTAL-PORTAL BRIDGING FIBROSIS ARE SEEN IN ASSOCIATION WITH THE
INFLAMMATION SUSPICIOUS FOR AUTOIMMUNE HEPATITIS
• Addendum 4/10:
– Scattered spirochetes are present in the biopsy, seen only
using the immunohistochemical stain. Liver involvement in
secondary syphilis has been associated with bile ductular
proliferation and associated neutrophils, both of which were
identified in this case in addition to the more typical features of
autoimmune hepatitis (plasma cell-rich lobular and interface
hepatitis).
11.
12. Some lessons from the case
• Syphilis can mimic many diseases
– the “Great Imitator”
– In this case - autoimmune hepatitis
• Current epidemic occurring disproportionately
in MSM, many with HIV infection
• STDs occur in persons over the age of 25 –
even over 55!
13. Return of the Great Imitator
Syphilis 2013
Charles Hicks, MD
Professor of Medicine
Duke University Medical Center
14. “Know syphilis in all its
manifestations and
relations, and all other
things clinical will be
added unto you.”
- Sir William Osler
15. History
The first description of syphilis occurred during
and after the 1494 siege of Naples.
Charles VIII invaded with 30,000 mercenary
soldiers who spread out over Europe after the
army was disbanded.
They brought with them a mysterious new
illness known first as “the Neopolitan disease,”
later as the “French sickness” and “great pox.”
During the 19th century the term syphilis became
universally accepted.
16. History
Origins of syphilis in Europe uncertain
Confused earlier with other diseases?
Columbian theory
Syphilis was endemic in New World
Spread to Europe from returning sailors
Whatever its origins, an aggressive form of
syphilis arose in the late 15th century -
“The Great Pox”
19. “In Englyshe Morbus Gallicus is named the
french pockes, whan than I was young they were
named the spanyshe pockes, the which be of
many kynds of the pockes…. The cause of these
impediments or infyrmytes doth come many
wayes…but specially it is taken when one pocky
person doth synne in lechary the one with
another. All the kinds of pockes be infectiouse.”
- Breviary of Healthe
Andrew Boord, 1547
20. Sick Report - Frigate “United States”
March 17, 1810
21. Dr. Julius Wagner-Jauregg
1927 Nobel Prize for Medicine for his discovery of “the therapeutic value
of malaria inoculation in the treatment of dementia paralytica”
22.
23. Syphilis - Penicillin
• 1943 - John Mahoney reported first trial of
penicillin in syphilis
• Four patients with early syphilis given
25,000 units penicillin IM q4h for 8 days
• Darkfield became negative within 16 hours
• Total dose was 1.2 million units - this
remains a magical number in syphilis
therapy to this date.
24.
25. Famous Persons with Syphilis
• Ivan the Terrible
• Peter the Great
• Catherine the Great
• Henry VIII of England
• Fredrich Nietzsche
• Albrecht Durer
• Benvenuto Cellini
• Guy de Maupassant
• Benito Mussolini
• Giovanni Cassanova
• Paul Gauguin
• Francisco Goya
• Vincent van Gogh
• John Keats
• Oscar Wilde
• Franz Schubert
• Moliere
• Heinrich Heine
26.
27. 1972 - Peter Buxton, a
PHS official, complained
to a reporter about an
ongoing study of syphilis
being conducted in black
men living in Alabama.
30. Tuskegee
• 1932: Study begins with about 600 black men
(more than 400 of whom had syphilis).
– Most are poor and uneducated
– Most from Tuskegee, Alabama, an area with the highest
syphilis rate in the U.S.
• Incentives for enrollment
– Free transportation to the hospital
– Free hot lunches
– Free medicine for any disease other than syphilis
– Free burial after autopsies were performed.
• By late 1940’s penicillin established as curative
for persons with syphilis, yet treatment not
provided to these men until decades later.
31. Tuskegee
• Understandably, the outrage was enormous,
especially in the African-American community
• Damage to the relationship with public health
community has been enduring and profound.
• This legacy of suspicion and distrust has made
public health and research efforts in HIV among
African-Americans extremely problematic.
– Belief among many African-Americans that HIV/AIDS is a
form of genocide that may have been created in a
laboratory does not seem so outlandish
• The Tuskegee study became for many blacks “a
symbol of their mistreatment by the medical
establishment, a metaphor for deceit, conspiracy,
malpractice, and neglect, if not outright racial
genocide.”
32. Remnants of the Tuskegee
Syphilis Study Effects on
University Freshmen: Yet a
Possible Barrier to Research
Participation?
Crystal B. Spivey, MPH, DrPH
March 9, 2004
Supported by: R24MD00151 NCMHD
33. Syphilis - Epidemiology
• Worldwide >12 million cases of syphilis annually
– 90% in the developing world
• U.S. cases peaked near the end of WWII, then fell
dramatically with the introduction of penicillin
• Mini-epidemic in late 1980s and early 1990s, then
declining to lowest level ever in 2000 (eradication?)
• Significant increase in cases thereafter which
continues….
36. Primary and Secondary Syphilis—Rates by Sex and
Male-to-Female Rate Ratios, United States, 1990–
2011
2011-Fig 38. SR
37. Primary and Secondary Syphilis—Rates by
Race/Ethnicity, United States, 2002–2011
2011-Fig 45. SR
38. Primary and Secondary Syphilis—Reported
Cases* by Sex, Sexual Behavior, and
Race/Ethnicity, United States, 2011
*Of the reported male cases of primary and secondary syphilis, 17.0% were missing sex of sex partner
information; 2.4% of sex partner data were missing race/ethnicity data.
†MSW=men who have sex with women only; MSM=men who have sex with men;
2011-Fig 47. SR
39. Primary and Secondary Syphilis—Rates by
Region, United States, 2002–2011
2011-Fig 39. SR
40.
41.
42.
43. Trends in Internet Use for Sexual Encounters
by MSM with Syphilis: 2001 - 2003
17.4
20.8
26.7
0
5
10
15
20
25
30
PercentInternetusers
2001 2002 2003
Report Year
(N=899)
LAC - DHS
44.
45. “The pleasure is
momentary, the position
ridiculous, and the expense
damnable”
-Attributed to Lord Chesterfield
46. Pathophysiology
Syphilis is caused by the
spirochete Treponema
pallidum.
It initiates infection after
gaining access to
subcutaneous tissues via
abrasions that occur
during sexual intercourse
Can initiate infection on
intact skin
47. Pathophysiology
After invading the
subcutaneous tissue the
organism establishes
the chancre.
Some organisms also
establish infection in
regional lymph nodes
during early local
replication.
48. Pathophysiology
Nearly all cases of syphilis are sexually acquired
(aside from congenital syphilis)
Transmission rate during primary and secondary
syphilis is about 30% and requires exposure to
open lesions – either primary chancre or
mucocutaneous lesions.
The incubation period varies but ranges from 10 –
90 days.
49. Clinical manifestations:
Primary syphilis
The initial clinical manifestations is the primary
chancre.
Usually painless, which distinguishes it from other
causes of genital ulcers: herpes simplex (genital
herpes) and Hemophilus ducreyi (chancroid).
May be indurated (collar button)
Most often heals without treatment over a period of
a few weeks.
50. Secondary syphilis
If untreated,
approximately 25% of
patients will go on to
develop systemic
symptoms
Rash
Fever
Headache
Malaise
Diffuse lymphadenopathy
Alopecia
53. Late vs. Latent syphilis
Latent syphilis refers to patients without symptoms
who have positive serologic testing for syphilis.
Early latent refers to duration less than one year
Late latent refers to duration greater than one year or of
unknown duration
Late or tertiary syphilis refers to the group of
clinical manifestations that may occur anywhere
between 1 and 30 years after infection when the
infection is not treated.
54. Tertiary syphilis
Patients may not have
experienced symptomatic
primary or secondary
syphilis prior to developing
tertiary syphilis
Most common
manifestations are central
nervous system, the
cardiovascular system, or
the skin and subcutaneous
tissues (gummas).
55. Neurosyphilis
Neurosyphilis refers to invasion of the CSF by T.
pallidum and can occur at any stage of disease
Early in the disease the most common manifestations
are asymptomatic meningitis, symptomatic meningitis,
and meningovascular disease.
Late in disease, the most common forms involve the
brain and spinal cord parenchyma (general paresis
[progressive dementia] and tabes dorsalis).
56. Asymptomatic neurosyphilis
By definition, no symptoms or signs of CNS
involvement
Can occur within weeks of infection
Characterized by lymphocytic pleocytosis typically <100 cells/µL, an
elevated protein concentration usually <100 mg/dL, a reactive VDRL, or
a combination of these.
CSF WBC count >10 lymphocytes per microliter + a protein
concentration >45 mg/dL in patients without HIV infection is suggestive
Reactive CSF-VDRL is diagnostic of neurosyphilis
In HIV-infected patients with a negative CSF VDRL the diagnosis is
challenging since a mild CSF pleocytosis and elevated protein are
relatively common in HIV-infected patients
57. Syphilis and HIV
HIV and syphilis are prevalent in the same risk groups,
particularly men who have sex with men (MSM)
The two infections can enhance the acquisition and transmission
of one other
Neurosyphilis may be more common in persons co-infected with
HIV; there have been many case reports of HIV+ patients
rapidly progressing from early syphilis to neurosyphilis
Failure of benzathine penicillin to cross blood-brain barrier
may be more problematic in HIV-infected persons with syphilis
58. Syphilis and HIV Infection
• More florid presentations of early syphilis
• More rapid progression to symptomatic
neurosyphilis after early infection
• Risk of benzathine penicillin treatment failure -
CNS
• Delayed seroconversion (RPR, FTA-Abs) in early
syphilis
• Potential for sero-reversion of treponemal
serology
• Unusually high titer non-treponemal serologic
results
Nonetheless, most cases managed as if HIV-
negative
59. Syphilis and HIV
Aberrant Serologic Testing for Syphilis
• HIV-positive patients with syphilis often have higher
titers of reagin antibodies than HIV-uninfected
individuals.
• However, some patients with very late stage HIV
infection have delayed or absent serologic responses
(i.e., false negative tests), or are more likely to lose
their reactivity after appropriate therapy.
• This variability is thought to reflect abnormally active
B-cell function during early HIV infection and B-cell
failure during late stage infection.
60. Syphilis and HIV
Aberrant Serologic Testing for Syphilis
• The rate of decline of nontreponemal titers
following successful therapy may also be
influenced by HIV co-infection, falling more slowly
in those with HIV infection.
• In a large, randomized prospective study of persons
with early syphilis, the HIV-coinfected group had a
higher rate of serologically defined treatment
failure.
• However, in this and other studies, all patients
responded clinically to treatment, suggesting that
the significance of the diminished serologic
response may be minimal.
61.
62. Diagnosis
T. pallidum cannot be grown
in culture, so other methods
have been used to identify
organisms
Dark field microscopy - direct
visualization of spirochetes taken
directly from lesions
Direct fluorescent antibody
testing was previously used –
detected T. pallidum-specific
antigens
Neither test currently available
More often, serologic tests
are used, traditionally:
Nontreponemal tests (VDRL and
RPR) measure reactivity of serum
from patients with syphilis to a
cardiolipin-cholesterol-lecithin
antigen. They measure IgG and
IgM antibodies and are reported
as titers.
Treponemal tests (FTA-ABS, MHA-
TP and TPPA) are based upon the
detection of antibodies directed
against treponemal cellular
components.
63.
64.
65.
66.
67.
68.
69.
70.
71. If asymptomatic, who needs LP?
Study of 239 patients with syphilis who
underwent LP analyzed to determine
predictors for neurosyphilis
Neurosyphilis defined as +CSF VDRL and/or
CSF WBC > 20 cells/ml
43 of 239 met diagnostic criteria. Predictors:
Serum RPR > 1:32
HIV infection with CD4 count < 350 cells /mm3
Marra et al. J Infect Dis 2004;189:369-76
74. Treatment
T. pallidum remains highly sensitive to penicillin and no resistance has been
reported to date despite several decades of use
75. Treatment
Successful therapy requires maintenance of prolonged low concentrations of
drug in infected tissues
Depot preparations such as benzathine penicillin accomplish this goal but
do not penetrate CNS
Standard therapy for primary, secondary, or early latent syphilis is
benzathene penicillin G (one dose 2.4 million units IM)
If the patient has had syphilis of greater than 1 year duration or if duration
is unknown, treatment should be benzathene penicillin G 2.4 million units IM
x 3 weekly doses
Neurosyphilis and ocular syphilis: 18 to 24 million units per day,
administered as 3 to 4 million units IV every four hours or continuous
infusion, for 10 to 14 days
76.
77. “Half of what we have taught
you is wrong. Unfortunately,
we do not know which half.”
– C. Sidney Burwell, M.D.
Address to the graduation class
Harvard Medical School