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CPC #6: Dark Voyage of the Fearless Eagle PowerPoint Presentation
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CPC #6: Dark Voyage of the Fearless Eagle

CPC #6: Dark Voyage of the Fearless Eagle

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CPC #6: Dark Voyage of the Fearless Eagle

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  1. CPC #6: Dark Voyage of the Fearless Eagle Bridging the Gap. Where Clinical and Basic Sciences Meet Louisa Balazs, MD, PhD Associate Professor of Pathology Khawar Shaikh, MD Fellow, Cardiovascular Diseases Karl T. Weber, MD Professor of Medicine

  2. A gentle summer breeze blew across the North Sea as the Fearless Eagle (der Adler), prepared to depart Hamburg in July, 1898.

  3. This steamer would make its first voyage to East Asia—a nonstop journey to Hong Kong that would take several months.

  4. Standing at the helm was Captain Tritthart, who barked out instructions to his crew.

  5. Young Dr. Bernhard Nocht made his way over to the captain. Nocht, a naval physician, would care for the ship’s crew while satisfying his wanderlust to visit distant shores. He reported that rations on board, including citrus fruit from Spain, baked bread, fresh vegetables, and fresh as well as canned meats, had passed his personal inspection. Further, all hired men were fit for the long journey. The arduous 60-day voyage on the high seas proved uneventful and import goods were delivered on time in early September.

  6. There followed a six-week stay in Hong Kong. The Captain kept the crew mindful of the ship’s time table. Asian exports had to be promptly loaded for the return voyage. As added incentive, he noted that by maintaining schedule the return voyage would reach Germany in time for the Christmas holiday.

  7. Tritthart also searched for men who could serve as stokers— fueling the ship’s hungry furnace.

  8. Twenty-three men would ultimately be hired, but only after Bernhard’s physical examination had pronounced them fit. All were of fine physique and Bernhard had found no evidence of communicable illnesses, such as measles, scarlatina, tuberculosis or smallpox; none had body lice, dermal eruptions or were jaundiced and none had cardiac murmurs, ascites, peripheral edema or neurologic deficits. To accommodate their dietary preferences Bernhard ordered crates of dried fish and white rice for the journey to Hamburg.

  9. The Chinese crew would not begin work until the steamer was back in Hamburg. They therefore would be passengers on this return voyage. By October 16 the Fearless Eagle was back at sea on its way to Hamburg. No illnesses appeared among European or Chinese crews during the uneventful 8-week voyage. By mid-December, and with the ship bsck in its Hamburg port, the Hong Kong-based crew was now actively involved in their physically demanding chores aboard the steamer.

  10. It was on December 26, that Bernhard found Song Yang and Li Ming had taken ill. Song Yang complained of poor appetite and malaise, nausea and generalized weakness. There was a loss of power in lower extremities with muscular atrophy and with a slow deliberate gait he hobbled about using ropes, hatches or dockhouses to steady himself. He further reported numbness and a prickling sensation to the soles of his feet.

  11. In recent days, Li Ming had taken ill with swollen facies and legs, a bounding, rapid pulse and neck vein distention. Bernhard arranged for both men to be admitted to a hospital. Li Ming died soon after admission. Captain Tritthart summoned Bernhard to his cabin to ascertain why these men had taken ill. Bernhard reported sadness and surprise at this unexpected turn of events. The Chinese crew were presumptively healthy and each had been carefully examined for illness prior to their hire.

  12. Food had not spoiled and water tanks were well maintained. The steamer was in good sanitary condition and did not harbor pestilence. If these men had been ill with infection when they came on board in Hong Kong, he could not discern what disease had a latency period of some 70 days and why others had not taken ill. Tritthart and Nocht could only guess at the possibilities, but infection seemed improbable. The Fearless Eagle departed for Boston on December 27.

  13. Out to sea but a few days, the steamer was engulfed by the first of several hurricane-like storms. The Chinese crew, barefoot and without proper clothing, was not prepared for these adverse conditions. Their exposure to the elements was constant as they traversed the flooded front deck several times daily to reach their living quarters. They frequently suffered upper respiratory infections.

  14. It was January 8, 1899, two weeks after their departure from Hamburg and 13 weeks since leaving Hong Kong, that Wong Shown reported ill. His legs, face and scrotum were swollen and he noted pains in both calves and chest. Bernhard found Wong to have a rapid but regular, bounding pulse; by percussion there was no evidence of cardiac enlargement. Over ensuing days, compressive dressings proved useful in reducing ankle and leg edema.

  15. Atrophy of leg and arm muscles became apparent and Wong developed a progressive paralysis of his lower extremities and remained confined to his quarters for the remainder of the journey. Perplexed and frightened, Bernhard struggled to contain his sense of helplessness. Crew members asked him to see Wong San on the evening of January 19. Wong San was the fourth member of the Chinese crew to fall ill, the third with swollen facies and leg edema.

  16. Pitting edema also involved the abdominal wall and thorax and there was percussion dullness in keeping with bilateral pleural effusions. Over ensuing days Nocht applied compressive leg dressings, warm poultices of aromatic scammony to the chest, while feet were inuncted with oils of cloves and mace mixed with oil of rose. Little seemed to help. His desperation growing, Bernhard turned to a decoction of Sarsaparilla roots in the hopes of dispelling the evil humor through sweat and urine.

  17. An extract of aloes was used as a cathartic. Despite these efforts, Wong San suddenly collapsed and died the evening of February 1. Yet another crew member, Wong Sui, was stricken on January 29 in the same way as his coworker. His symptoms were less advanced, but his fear overwhelming. Violent storms again appeared to further prolong the journey. On February 8, Wong Sui, his feeble voice barely audible, attempted to speak with fellow crew members as they left guard duty.

  18. He was found dead in his berth an hour later. Bernhard noted that he had developed marked edema of face, trunk and legs. Between February 16 and mid-March, 1899, five additional members of the Chinese crew would be stricken with the ailment that featured facial and peripheral edema; most had rapid heart rate. All told and since the departure of the Fearless Eagle from Hong Kong on October 16, ten cases had appeared; 5 had not survived.

  19. By early April and out of desperation, Captain Tritthart arranged for the remainder of the Chinese crew to be placed aboard a steamer bound for East Asia and so ended the epidemic aboard this steamer.

  20. The 54-day voyage to Boston had taken longer than expected. Exhausted and perplexed, Bernhard Nocht and Captain Tritthart sat down to survey the epidemic and circumstances that had befallen their hardworking Chinese crew. There had been several intrinsic difficulties. First, the crew was reluctant to bring their ailments to attention for fear of retribution. As a result, they only presented when their illness and symptoms were far advanced. Second, they did not trust the European physician.

  21. Third, detailed clinical evaluation had been hampered by the weather, the crew’s obligatory responsibilities and inadequate quarters for health care. Finally, Bernhard admitted that his understanding of the illness was hindered by limited onboard medical literature. Nocht provided his perspective. He focused on three areas: the crew’s living conditions, the climate encountered during the voyage, and the crew’s nutritional status.

  22. The men had been provided larger-than-recommended quarters that were well ventilated and this was true for journeys between Hong Kong and Hamburg and Hamburg to Boston. No prior Asian inhabitants had occupied these quarters. Tritthart added it was policy after each 6-week voyage, that living quarters be disinfected; indeed prior to leaving Hamburg in December they had also been painted. They concluded living conditions could not have been contributory. This could not be a “place infection,” an illness endemic to a disease-laden ship.

  23. The journey between Hamburg and Boston had been prolonged by adverse weather and members of the Chinese crew were not properly clothed and regularly had taken ill with common colds. Could this have made them more susceptible to the illness? Drinking water was considered noncontributory. It was available to all sailors and was replenished during each voyage at ports frequented regularly by many vessels.

  24. Despite recommendations for a diverse diet, the Chinese crew preferred their own rations that included fish, white rice and various spices. A separate kitchen had provided them privacy and the opportunity to prepare their dietary intake according to custom and preference. Rice purchased for the crew was considered to be of the highest quality.

  25. The same could not be said for the fish. The crew had preferred half-cooked fish and dried fish. As adverse weather prolonged the voyage, rations became low. Discovery of spoiled fish, which the crew may have consumed, led to prompt disposal. The crew rebuked recommended European fare even though none of the Europeans aboard had taken ill. The importance of fish to the epidemic could therefore not be discounted. What is your diagnosis and what is its causality?

  26. Case I & II • Song Yang: • Poor Appetite, Malaise, nausea, generalized weakness (constitutional) • Loss of power in LE, gait abnormality, numbness and prickling sensation in distal extremity (peripheral nerve symptoms) • Li Ming : • Poor appetite, malaise, nausea, generalized weakness (constitutional) • Loss of power in LE, gait abnormality, numbness and prickling sensation in distal extremity (peripheral nerve symptoms) • Swelling of face & legs, bounding pulse, neck veins (hyperdynamic circulation and volume overload • Rapidly fatal

  27. Case III & IV • Wong Shown: • Swelling of face & legs (volume overload) • Pains in calves & chest • Bounding pulse, no cardiomegaly, (hyperdynamic circulation) • Progressive paralysis of lower extremities • Wong San: • Swollen facies + leg edema • Bilateral pleural effusion • Rapidly fatal

  28. Differential diagnosis: Part I • Infectious Processes: Less likely latency of 70 days, no members of the European crew were involved (race specific), Hepatitis: No jaundice, neuropathy • Poisoning: Arsenic: Burning of fossil fuels and consumption of food & smoking tobacco treated with Arsenic containing pesticides. Although it can cause peripheral neuritis and quadriplegia and delayed cardiomyopathy – also characteristic are nail/skin changes and other keratin containing tissue changes, vasospasm-black foot • Amyloidosis: Peripheral neuritis and heart failure. Rapid course and absence of chronic disease. Race specific. • Syphilis, Tertiary with AR and Tabes dorsalis (sporadic, healthy at screening) • Chronic alcoholism

  29. Differential Diagnosis: Part II Storage diseases: Muscle glycogenosis (phosphorylase kinase defficiency) etc. Mucopolysaccharidosis Mitochondrial diseases • industrial agents--especially solvents • heavy metals (lead, arsenic, mercury, etc.) • Nutritional deficiencies: White rice, dried fish

  30. Thiamine deficiency

  31. Thiamine • "There is present in rice polishings a substance different from protein and salts, which is indispensable to health and the lack of which causes nutritional polyneuritis" • Christian Eijkman and Gerrit Grijns, 1906

  32. Thiamine • Thiamine diphosphate (pyrophosphate), serves as a co-enzyme for several reactions that cleave C-C bonds, e.g., oxidative decarboxylation of alpha-keto acids (pyrovate & Leucine, isoleucine, & reactions in pentose monophosphate pathway. Many features of thiamine deficiency are result of inhibition of these enzymatic pathways or accumulation of their metabolites. • Thiamine has specific role in neurons independent of metabolism.Thiamine & its esters are present in axonal membranes & electrical stimulation of nerves effect hydrolysis & release of thiamine diphosphate and triphosphate.

  33. Thiamine • Vitamin is wide spread amongst a number of food sources esp. vegetables, outer layers of cereal grains (hence machine milled rice is a poor source), it is present in animal sources as phosphate esters. A substantial loss of vitamin takes place during cooking above 100°C. • Requirements increase in pregnancy, lactation, thyrotoxicosis and fever. Accelerated loss may occur with diuretic therapy, dialysis, diarrhea, malabsorption states, alcoholism, chronic malnutrition & folate deficiency

  34. BeriBeri • Two major manifestations of Th. Def. involve cardiovascular system (wet beriberi) & nervous system (dry beriberi). A typical patient has mixed symptoms involving both cardiovascular and nervous system, relative preponderance of these symptoms is related to duration and severity of deficiency. • Severe physical exertion, high carbohydrate intake & moderate chronic defficiency favor wet beriberi, whereas an equal deficiency with caloric restriction & relative inactivity favors development of dry beriberi.

  35. Cardiovascular manifestations • Three major physiologic derangements are seen. Peripheral vasodilatation leading to a high output state. Retention of sodium and water leading to edema. Biventricular myocardial failure.

  36. Cardiovascular manifestations • Acute fulminant cardiovascular (Shoshin) beriberi, myocardial lesion is the central feature of a course in which dyspnea, restlessness, and anxiety eventuates into acute cardiovascular collapse & death within hours to days. Physical findings include stocking-glove cyanosis, tachycardia, marked cardiomegaly, hepatomegaly, arterial bruits & neck vein distention. Because of fulminant course edema may be minimal. Thiamine administration may restore BP but low output failure may supervene during treatment.

  37. Neurologic Involvement • Three forms of nervous system involvement occur. Peripheral neuropathy, Wernicke’s encephalopathy (cerebral beriberi) & the Korsakoff syndrome. • The neuropathy may or may not be painful characterized by a symmetric impairment of sensory, motor and reflex function that affects predominantly the distal parts of limbs. Histologic lesion is a non-inflammatory degeneration of myelin sheaths. There is no meaningful clinical distinction between this and alcoholic neuropathy.

  38. Treatment • Drug Category: Vitamins -- Organic substances required by the body in small amounts for various metabolic processes. Vitamins may be synthesized in small or insufficient amounts in the body or not synthesized at all, thus requiring supplementation. • Drug NameThiamine hydrochloride (Thiamilate) -- Essential coenzyme that combines with ATP to form thiamine pyrophosphate. Dosage forms include a parenteral injection (l00 mg/mL) and tablets.

  39. Sarsaparilla • Sarsaparilla is the dried root of Smilax ornata, Hook. f. (N.O. Smilaceae), a climbing plant growing in Costa Rica. • Action and Uses.—Sarsaparilla is used in the treatment of chronic rheumatism, skin diseases, and in syphilis. It is extremely doubtful whether it exerts any action in these conditions, and its chief use is as a vehicle for the administration of mercury and potassium iodide.

  40. Thiamine deficiency Macroscopic and microscopic considerations

  41. External examination • Mild malnutrition • Anasarca • Dilated neck large vessels • Pupils have even diameter • Normal antero-posterior thoracic diameter • Protruding abdomen • Atrophic lower extremity musculature

  42. Internal examination • Hydrothorax (bilateral, straw-colored transudate, 300 ml) • Hydropericardium (150 ml clear, transudate) • Ascites (1000 ml, clear, straw-colored) • Cardiomegaly, hepatosplenomegaly

  43. Cardiovascular system • Heart: normal to severely enlarged • Dilated right and left ventricles • Globular shape (four-chamber dilation) • Pale flabby myocardium • Mural thrombi in atria

  44. Cardiovascular system • Patent coronary arteries • No evidence of myocardial infarct • No aortic and peripheral arteriosclerosis • Microscopy: mild myocardial hypertrophy • Negative for necrosis or fibrosis • No evidence of myocarditis and cardiomyopathy

  45. Cardiomegaly and biventricular dilation

  46. Heart - hypertrophy and ventricular dilation

  47. Myocardium, H&E stain

  48. Respiratory system • Tracheal and bronchial mucosa covered by frothy fluid • Smooth and glistening pleural surface • Heavy, dark-purple lung parenchyma • Negative for consolidation • Homogeneous dark purple cut surface • Brownish fluid on pressure

  49. Acute pulmonary congestion

  50. Pulmonary edema