[Pathological profile of S.P. Botkin infectious hospital during the siege of Leningrad (1941-1944)]. / Patologo-anatomicheskii profil' infektsionnoi bol'nitsy im. S.P. Botkina v gody blokady Leningrada (1941­1944 gg.).

The results of autopsies performed in the pathological department of the Infectious Diseases Hospital named after. S.P. Botkin during the siege of Leningrad (from September 8, 1941 to January 27, 1944). The structure of diseases of the deceased varied during different periods of the siege of Leningrad. In the first period (September-December 1941), diphtheria, dysentery, measles, typhoid fever, and scarlet fever prevailed among the diseases. The most common causes of death in the second period (April-December 1942) were typhus, dysentery, tuberculosis, lobar pneumonia, and typhoid fever. Nosological structure in the third period of the blockade (January 1943 - January 1944): tuberculosis, dysentery, cachexia, lobar pneumonia, infectious jaundice. The discrepancy between clinical and morphological diagnoses is most often noted for the following nosology: pulmonary tuberculosis, typhoid fever, pneumonia, stomach and hepatopancreatobiliary cancer, measles, influenza. The first period of the blockade was distinguished by a high specific proportion of examination of children's bodies - 51.2% of all autopsies; in subsequent periods, the specific share of autopsies of deceased adults (20-59 years) increased to 76.2%. The difference in the nosological structure and age groups of those who died during different periods of the siege of Leningrad was determined by the epidemiological situation in the city, social and living conditions and medical and organizational factors. Conducted in the pathological-anatomical department of the hospital named after. S.P. Botkin during the siege of Leningrad, pathological studies made it possible to timely establish the causes of deaths and identify the peculiarities of the course of infectious diseases against the background of cachexia. Regularly held clinical and anatomical conferences contributed to the reduction of defects in the diagnosis and treatment of infectious diseases.

[Analysis of fatal outcomes of meningococcal infection in adults].

Clinical characteristics and pathomorphological manifestations in 69 patients aged 18 to 86 years with a fatal outcome of the disease were examined in order to analyze the causes of severe course and high mortality of generalized forms meningococcal infection. It was found that the main clinical form was meningococcemia (90%), in the majority in combination with meningitis (52%). The fulminant course in 77% of patients with meningococcal sepsis manifested itself as a sudden onset, rapid development of typical symptoms. Hemorrhagic exanthema was detected on the first day of meningococcemia. The leading complications and critical conditions were infectious-toxic shock, disseminated intravascular coagulation and acute adrenal insufficiency (Waterhouse-Friederiksen syndrome). The severe course of meningitis (in 10%) led to the development of cerebral coma, the morphological substrate of which was edema - swelling of the brain.

[Vsevolod Dmitrievich Zinserling. (On the occasion of the 130th anniversary of his birth)]. / Vsevolod Dmitrievich Tsinzerling. (K 130-letiyu so dnya rozhdeniya).

IVsevolod Dmitrievich Zinserling was born on September 20, 1891, in St. Petersburg. His father, Dmitri Petrovich Zinserling, a descendant of immigrants from the south of Germany or Switzerland, who received hereditary nobility, worked all his life as a teacher of mathematics and, as an inspector of the famous Gurevich Gymnasium, had the rank of actual state councilor. Dmitry Petrovich was also the author of scientific research on the history of mathematics in ancient Egypt, manuals on statistics, and algebra textbook, which was republished many times. His mother, Olga Ivanovna (nee Semenova), ran the household and raised four children. There was a creative atmosphere in the family, all had artistic talents, loved and knew nature well. The elder brother Boris Zinserling, a graduate of the Academy of Fine Arts, an officer, after the Civil War, found himself in Warsaw, where he became a professor and author of projects to restore many architectural masterpieces in the postwar period. His younger brother Yuri (George) Zinserling, a doctor of biological sciences, a botanist, one of the founders of a new scientific trend - geobotany, was arrested in 1938 when he was acting director of the Botanical Institute and soon died in custody. His sister Nina was an artist who died at a young age.

[Pathological anatomy of tuberculosis in the presence of human immunodeficiency virus infection]. / Patologicheskaia anatomiia tuberkuleza na fone infektsii, vyzvannoi virusom immunodefitsita cheloveka.

Tuberculosis occupies a leading position among secondary infections in the structure of mortality in HIV-positive patients. Moreover, the concurrence of these diseases frequently makes a morphological diagnosis most difficult due to the atypical course of tuberculosis (TB) in the presence of immunosuppression. AIM: to assess the clinical and morphological characteristics of concurrent TB/HIV infection. MATERIAL AND METHODS: An autopsy material obtained from the S.P. Botkin Clinical Infectious Diseases Hospital (CIDH) in 2018 was analyzed. Eight samples stained with hematoxylin and eosin, Ziehl-Neelsen carbol-fuchsin, auramine-rhodamine were thoroughly examined, followed by fluorescent microscopy; an immunohistochemical (IHC) study was performed. RESULTS AND DISCUSSION: 736 autopsies made at the S.P. Botkin CIDH in 2018 revealed 357 deaths from HIV infection; 86 (24%) cases of which were caused by concurrent HIV/TB infection. All the cases showed an extremely diverse and heterogeneous pattern that considerably differed from that of classical granulomatous inflammation in tuberculosis. Ziehl-Neelsen staining could demonstrate single clusters of acid-resistant bacteria with a total of not more than 1000 in the specimen of predominantly rod-shaped bacteria. Auramine-rhodamine staining revealed focal clusters of mycobacteria with a total of 1000 to 2000 in the specimen of predominantly rod-shaped and coccoid bacteria. An IHC study identified clusters of mycobacteria with a total of more than 2000 in the sample, which were characterized by a moderate variety of shapes: rods, cocci, granules, clavate, and branched ones. Mycobacteria were present extracellularly in all the studied cases. CONCLUSION: Tuberculosis holds the most important place in the pattern of causes of death in HIV infection, accounting for 24%. The lifetime diagnosis of tuberculosis remains not entirely satisfactory. The alterative component of inflammation more often predominates, although without completely losing the ability to form granulomas. The concurrence of different morphological forms of tuberculosis makes it highly desirable to clarify and/or supplement the existing classifications. None of the methods used to detect Mycobacterium tuberculosis in the tissues could reveal the intracellular localization of the pathogen. Most mycobacteria had a typical rod-shaped morphology.

[Neurogenesis in the adult human brain: morphological aspects]. / Morfologicheskie aspekty neirogeneza v golovnom mozge vzroslogo cheloveka.

The high prevalence of diseases leading to brain injury disability makes it extremely relevant to study the various mechanisms of neurorehabilitation, among which neurogenesis has recently received a great attention. Over the past 20 years, there has been ample evidence for neurogenesis in the adult animal brain. Despite the fact that the prenatal development of the human brain has been thoroughly studied, the number of works on the process by which new neurons form in the adult human brain is not so large. This review devoted to the investigations of neurogenesis in the adult human brain includes data on changes in neurogenesis with age in neurodegenerative diseases, strokes, epilepsy, various addictions, traumatic injuries, and natural and drug regulation. The conclusion lists the issues on which there is an agreement or conflicting views in the literature and indicates the unanswered aspects of the problem.

[The informative value of various methods for identifying acid-fast bacilli in relation to the degree of tuberculosis process activity]. / Informativnost' razlichnykh metodov identifikatsii kislotoustoichivykh mikobakterii v zavisimosti ot stepeni aktivnosti tuberkuleznogo protsessa.

Carbol fuchsin (Ziehl-Neelsen) staining is a major method used since the late nineteenth century to detect Mycobacterium tuberculosis in the tissues. At the same time, the number of mycobacteria does not frequently show a clinical and morphological correspondence to the activity of the infectious process. OBJECTIVE: To reveal the morphological characteristics of Mycobacterium tuberculosis in patients with long-lasting tuberculosis. MATERIAL AND METHODS: Twenty-four autopsies of verified fibrous-cavernous tuberculosis were examined. Paraffin sections were stained with hematoxylin and eosin, carbol fuchsin (Ziehl-Neelsen), or auramine-rhodamine (followed by luminescence microscopic examination); an immunohistochemical (IHC) study with serum to PAV (Protein antigen B) was conducted. RESULTS AND DISCUSSION: The changes characteristic of progressive tuberculosis were revealed in all the cases. The Ziehl-Neelsen staining revealed isolated clusters of acid-fast bacilli (a total of 1,000 in less than 10 fields of view). When stained with auramine-rhodamine, the number of found mycobacteria proved to be significantly larger (a total of 1,000 to 10,000 in 10-50 fields of view) and that was greatest in the IHC study (a total of over 10,000 in more than 50 fields of view). At the same type, all types of studies revealed that the localization of mycobacteria was exclusively extracellular. The Ziehl-Neelsen staining indicated that the proportion of typical bacilli was much higher (85-95%; mean 88.13±2.14) than that (50-85%; mean 64.38±4.24%) identified when stained with auramine-rhodamine and even more significantly more than that (50-70%; mean 57.29±2.78%) detected during the IHC study. The indicators were equally different for the atypical morphological forms of mycobacteria identified in minimal quantities by the Ziehl-Nielsen staining and in large quantities by fluorescence and IHC studies. CONCLUSION: There is evidence for the ability of mycobacteria to have morphological polymorphism and for the need to clarify the pathogenesis of tuberculosis.

[Clinical and morphological correlations in occult hepatitis B]. / Kliniko-morfologicheskie sopostavleniia pri okkul'tnom gepatite B.

Occult hepatitis B (ОHB) characterized by the absence of blood HBsAg attracts the attention of specialists of different profiles; however, its clinical morphological aspects have not been practically studied. AIM: to estimate the proportion of OHB in the structure of fatal outcomes in chronic viral hepatitis (CVH) and to characterize its clinical course and structural changes on autopsy materials. MATERIAL AND METHODS: A total of 455 autopsy cases of CVH were examined for its etiology in the S.P. Botkin Clinical Hospital of Infectious Diseases in 2014-2016. An in-depth prospective clinical analysis was made to investigate 28 cases of OHB in the stage of decompensated liver cirrhosis, which had subsequently culminated in death. The criteria of inclusion were history data and clinical symptoms of CVH in the detection of markers for hepatitis A, C, and D and HIV in serum HBcAb in the absence of HBsAg. HBsAbs were also determined. Along with the traditional morphological examination, immunohistochemistry (IHC) for HBsAg and HBcAg was carried out. RESULTS: There were 108 CVHB cases (23.7% of the total cases of CVH), including 77 OHB cases (71.3% of those of CVHB) while HBsAg was not determined. HBsAb-negative patients were more often observed to have clinical signs of jaundice (p<0.05) and skin itching (p<0.05). Dyspepsia and hemorrhagic manifestations prevailed in patients with HBsAb (more than 10 IU/l) (p<0.05). All the cases were found to have characteristic morphological signs of CVH, including intranuclear inclusions and nuclear polymorphism in 10.7% of deaths. There was an IHC-positive reaction to VHB antigens in 28.6% of the patients and a doubtful reaction in 25.0%. CONCLUSION: Serum НВсAb may serve as a diagnostic marker for HBV infection. Clinical and morphological correlations enabled the authors to state that CVHB was present in all cases in the absence of serum HBsAg in the patients.

[Morphological diagnosis of tuberculosis under present-day conditions].

The paper presents general statistical data on morbidity and mortality rates of tuberculosis, which show positive trends in recent years, with exception of those of its concurrence with HIV infection. The tasks of the morphological diagnosis of tuberculosis are divided into 4 groups: 1) to refine approaches to detecting mycobacteria in tissues; 2) to optimize the postmortem diagnosis of tuberculosis; 3) to optimize the lifetime differential diagnosis of tuberculosis and to develop methods for predicting its course; 4) to study the pathogenesis of tuberculosis from the standpoint of modern views on an infectious process. The data suggesting that the tissue forms of mycobacteria, the types of inflammatory responses, and the specific features of the pathogenesis of tuberculosis call for further investigations are given. To establish the real role of nontuberculous mycobacteria, to study the likelihood that the patient will be superinfected with other M. tuberculosis genotypes, and to elaborate a uniform (clinical, pathogenetic, and morphological) classification of tuberculosis should be also regarded as the most important tasks in its morphological examination.

[Postmortem diagnosis of influenza during its epidemic and interepidemic periods].

OBJECTIVE: to assess the potential role of influenza virus in fatal pneumonia during the epidemic and interepidemic periods. MATERIAL AND METHODS An immunohistochemical method was used to clinically and morphologically analyze 40 fatal outcomes of acute pneumonias in 2009-2013. Laboratory tests could not establish the diagnosis of influenza in 20 cases of the study group with clinical and/or morphological pattern of this illness. Seventeen cases occurred during the epidemic period (autopsies from November 2009 to January 2010) and the seasonal rise of morbidity; 3 cases were observed during the interepidemic period. A control group was additionally formed from 20 cases with neither clinical nor further morphological evidence of suspected influenza in the presence of pneumonia in both the epidemic and interepidemic periods. RESULTS: In the study group, influenza virus nucleoprotein was detected by immunohistochemistry (IHC) in the bronchial epithelial cells with the signs of cytopathic changes in half of the cases and that in the alveolocytes in 30%. Sporadic cases displayed a positive IHC response of blood vessel endothelial cells, which was attended by staining of the epithelium and macrophages. The maximum disease periods with the virus nucleoprotein being detected by IHC in the macrophages doubled those in the epithelial cells (40 versus 22 days). The control group showed a large number of cases with a positive macrophage response that was approximately similar to that in the study group. Despite the frequent detection and intensive staining of macrophages, they demonstrated no cytopathic changes, which can be explained by the low virulence persistence of influenza virus in the macrophages. CONCLUSION: These investigations showed the role of influenza virus in the occurrence of additional deaths in the epidemic period and a possible fatal outcome in the interepidemic period.

Fatal respiratory tract diphtheria apparently caused by nontoxigenic strains of Corynebacterium diphtheriae.

A major diphtheria epidemic affecting the whole population of St. Petersburg started in 1990. During the period of 1991 to 1995, 4600 patients with clinical respiratory tract diphtheria were treated in Botkin's Hospital. From 112 (2.4%) of these patients only a nontoxigenic strain of Corynebacterium diphtheriae was isolated. Three patients with this strain who were suffering from clinical disease consistent with classical toxic diphtheria died. All had myocarditis, two had asphyxia due to membrane formation in the lower respiratory tract, and one had severe polyneuritis. In two patients the causative agent was of the biotype mitis and in the third intermedius, whereas the prevailing epidemic strain was of the biotype gravis. As the clinical presentation of the disease in the three patients who died was typical of toxic diphtheria, it is considered likely that the immunodiffusion test for toxin production in vitro may fail to detect strains of Corynebacterium diphtheriae producing toxin in vivo.

Study of brain and vascular plexus gangliosides in meningoencephalitis of various etiology.

The content of brain and vascular plexus gangliosides and their composition have been studied in 15 cases of meningoencephalitis of various etiology and degree of disease. The most pronounced decrease of ganglioside concentration was found in brain of children, who died from herpes virus infection. Decrease of ganglioside content was revealed in brain grey matter of patients with influenza virus or meningococcus infection, but not in cases of mycoplasma infection. These data provide evidence of nerve cell destruction due to meningoencephalitis of various etiology. The biochemical data obtained are in good agreement with the results of the brain of children infection by herpes virus (increase of GD1b content in grey matter). Ganglioside content in vascular plexes of patients with meningoencephalitis was found to be, on the contrary, much higher (ca 4 times) than in the controls. The higher the lesion of choroid plexes in meningoencephalitis is, the higher the ganglioside content in them is.

Extrapulmonary lesions in influenza.

The authors, having investigated 270 autopsied cases of influenza in children, reported the possibility of a hematogenic virus dissemination from the respiratory system. In the acute stage of the disease the antigen of influenza was revealed in the liver, intestine, kidneys, brain and other organs with adequate regularity. The antigen was localized in the epithelial cells and also endothelial, ependymal and some other cells. The latter were partly accompanied by specific structural changes similar to those that occur in the respiratory system in the presence of the same disease. Besides, degenerative, exudate and, now and then, proliferative and regenerative changes which were not specific for influenza, have been found in all affected organs. Of particular interest were the results of brain study, in which viral particles were revealed by electron microscopic examination in chronic inflammatory lesions. In the experimental study carried out on 180 newborn mice by means of histological, immunofluorescent, serological and virological methods was proven the possibility of generalization of influenza, and some aspects of the pathogenesis were discussed.