scholarly journals Clinical recovery of Macaca fascicularis infected with Plasmodium knowlesi

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mariko S. Peterson ◽  
Chester J. Joyner ◽  
Jessica A. Brady ◽  
Jennifer S. Wood ◽  
Monica Cabrera-Mora ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tissue Damage ◽  
Macaca Fascicularis ◽  
Plasmodium Knowlesi ◽  
Clinical Signs ◽  
Parasite Load ◽  
Blood Chemistry ◽  
Severe Anaemia ◽  
Chronic Infections ◽  
Tissue Samples

Abstract Background Kra monkeys (Macaca fascicularis), a natural host of Plasmodium knowlesi, control parasitaemia caused by this parasite species and escape death without treatment. Knowledge of the disease progression and resilience in kra monkeys will aid the effective use of this species to study mechanisms of resilience to malaria. This longitudinal study aimed to define clinical, physiological and pathological changes in kra monkeys infected with P. knowlesi, which could explain their resilient phenotype. Methods Kra monkeys (n = 15, male, young adults) were infected intravenously with cryopreserved P. knowlesi sporozoites and the resulting parasitaemias were monitored daily. Complete blood counts, reticulocyte counts, blood chemistry and physiological telemetry data (n = 7) were acquired as described prior to infection to establish baseline values and then daily after inoculation for up to 50 days. Bone marrow aspirates, plasma samples, and 22 tissue samples were collected at specific time points to evaluate longitudinal clinical, physiological and pathological effects of P. knowlesi infections during acute and chronic infections. Results As expected, the kra monkeys controlled acute infections and remained with low-level, persistent parasitaemias without anti-malarial intervention. Unexpectedly, early in the infection, fevers developed, which ultimately returned to baseline, as well as mild to moderate thrombocytopenia, and moderate to severe anaemia. Mathematical modelling and the reticulocyte production index indicated that the anaemia was largely due to the removal of uninfected erythrocytes and not impaired production of erythrocytes. Mild tissue damage was observed, and tissue parasite load was associated with tissue damage even though parasite accumulation in the tissues was generally low. Conclusions Kra monkeys experimentally infected with P. knowlesi sporozoites presented with multiple clinical signs of malaria that varied in severity among individuals. Overall, the animals shared common mechanisms of resilience characterized by controlling parasitaemia 3–5 days after patency, and controlling fever, coupled with physiological and bone marrow responses to compensate for anaemia. Together, these responses likely minimized tissue damage while supporting the establishment of chronic infections, which may be important for transmission in natural endemic settings. These results provide new foundational insights into malaria pathogenesis and resilience in kra monkeys, which may improve understanding of human infections.

scholarly journals Clinical recovery of Macaca fascicularis infected with Plasmodium knowlesi

2021 ◽  
Author(s):  
Mariko S. Peterson ◽  
Chester J Joyner ◽  
Jessica A. Brady ◽  
Jennifer S Wood ◽  
Monica Cabrera-Mora ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tissue Damage ◽  
Macaca Fascicularis ◽  
Plasmodium Knowlesi ◽  
Clinical Signs ◽  
Parasite Load ◽  
Blood Chemistry ◽  
Severe Anaemia ◽  
Chronic Infections ◽  
Tissue Samples

Background Kra monkeys (Macaca fascicularis), a natural host of Plasmodium knowlesi, control parasitaemia caused by this parasite species and escape death without treatment. Knowledge of the disease progression and resilience in kra monkeys will aid the effective use of this species to study mechanisms of resilience to malaria. This longitudinal study aimed to define clinical, physiological and pathological changes in kra monkeys infected with P. knowlesi, which could explain their resilient phenotype. Methods Kra monkeys (n = 15, male, young adults) were infected intravenously with cryopreserved P. knowlesi sporozoites and the resulting parasitaemias were monitored daily. Complete blood counts, reticulocyte counts, blood chemistry and physiological telemetry data (n = 7) were acquired as described prior to infection to establish baseline values and then daily after inoculation for up to 50 days. Bone marrow aspirates, plasma samples, and 22 tissue samples were collected at specific time points to evaluate longitudinal clinical, physiological and pathological effects of P. knowlesi infections. Results As expected, the kra monkeys controlled parasitaemia and remained with low-level, persistent parasitaemias without antimalarial intervention. Unexpectedly, early in the infection, fevers developed, which ultimately returned to baseline, as well as mild to moderate thrombocytopaenia, and moderate to severe anaemia. Mathematical modeling and the reticulocyte production index indicated that the anaemia was largely due to the removal of uninfected erythrocytes and not impaired production of erythrocytes. Mild tissue damage was observed, and tissue parasite load was associated with tissue damage even though parasite accumulation in the tissues was generally low. Conclusions Kra monkeys experimentally infected with P. knowlesi sporozoites presented with multiple clinical signs of malaria that varied in severity among individuals. Overall, the animals shared common mechanisms of resilience characterized by controlling parasitaemia 3-5 days after patency, and controlling fever, coupled with physiological and bone marrow responses to compensate for anaemia. Together, these responses likely minimized tissue damage while supporting the establishment of chronic infections, which may be important for transmission in natural endemic settings. These results provide new foundational insights into malaria pathogenesis and resilience in kra monkeys, which may improve understanding of human infections.

scholarly journals Morphological Changes in the Bone Marrow of the Dogs with Visceral Leishmaniasis

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Claudia Momo ◽  
Ana Paula Prudente Jacintho ◽  
Pamela Rodrigues Reina Moreira ◽  
Danísio Prado Munari ◽  
Gisele Fabrino Machado ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Visceral Leishmaniasis ◽  
Morphological Changes ◽  
Clinical Signs ◽  
Parasite Load ◽  
Systemic Circulation ◽  
Clinical Group ◽  
Leishmania Chagasi ◽  
Control Center ◽  
A Site

The aim of this study was to evaluate the most frequent lesions in the bone marrow of dogs naturally infected byLeishmania (Leishmania) chagasi.Thirty-three dogs sacrificed at the Zoonosis Control Center of Araçatuba, a municipality endemic for visceral leishmaniasis (VL), were used. The animals were classified as asymptomatic, oligosymptomatic, and symptomatic groups. At the necropsy, bone marrow samples were collected from the femur, fixed, processed, and stained with hematoxylin and eosin. The lesion intensity was classified as mild, moderate, or severe. The parasite load was determined using immunohistochemistry. The most important lesions consisted of multifocal to diffuse granulomas, megakaryocytic dysplasia, and medullary aplasia. There were no statistical differences between the three clinical groups regarding parasite load and lesion intensity. Asymptomatic dogs also presented high parasitism in the bone marrow as dogs with clinical signs of VL. It was concluded that, regardless of clinical group, the bone marrow is a site for multiplication ofLeishmania chagasi. Possibly, the bone marrow dysplasia may arise from the presence of many parasitized and activated macrophages in this organ. Consequently, it affects the profile of hematopoietic cells in the bone marrow and systemic circulation.

scholarly journals Frequency of co-seropositivities for certain pathogens and their relationship with clinical and histopathological changes and parasite load in dogs infected with Leishmania infantum

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247560
Author(s):  
Valéria da Costa Oliveira ◽  
Artur Augusto Velho Mendes Junior ◽  
Luiz Claudio Ferreira ◽  
Tatiana Machado Quinates Calvet ◽  
Shanna Araujo dos Santos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Leishmania Infantum ◽  
Dirofilaria Immitis ◽  
Clinical Signs ◽  
Parasite Load ◽  
Inflammatory Cells ◽  
Canine Leishmaniosis ◽  
Conventional Pcr ◽  
Serum Samples ◽  
Histological Changes

In canine leishmaniosis caused by the protozoan Leishmania infantum, little is known about how co-infections with or co-seropositivities for other pathogens can influence aggravation of this disease. Therefore, the objectives of this study were to evaluate the frequency of co-infections with or co-seropositivities for certain pathogens in dogs seropositive for L. infantum and their relationship with clinical signs, histological changes and L. infantum load. Sixty-six L. infantum-seropositive dogs were submitted to clinical examination, collection of blood and bone marrow, culling, and necropsy. Antibodies against Anaplasma spp., Borrelia burgdorferi sensu lato, Ehrlichia spp. and Toxoplasma gondii and Dirofilaria immitis antigens were investigated in serum. Samples from different tissues were submitted to histopathology and immunohistochemistry for the detection of Leishmania spp. and T. gondii. Quantitative real-time PCR was used to assess the L. infantum load in spleen samples. For detection of Coxiella burnetii, conventional PCR and nested PCR were performed using bone marrow samples. All 66 dogs tested positive for L. infantum by qPCR and/or culture. Fifty dogs (76%) were co-seropositive for at least one pathogen: T. gondii (59%), Ehrlichia spp., (41%), and Anaplasma spp. (18%). Clinical signs were observed in 15 (94%) dogs monoinfected with L. infantum and in 45 (90%) dogs co-seropositive for certain pathogens. The L. infantum load in spleen and skin did not differ significantly between monoinfected and co-seropositive dogs. The number of inflammatory cells was higher in the spleen, lung and mammary gland of co-seropositive dogs and in the mitral valve of monoinfected dogs. These results suggest that dogs infected with L. infantum and co-seropositive for certain pathogens are common in the region studied. However, co-seropositivities for certain pathogens did not aggravate clinical signs or L. infantum load, although they were associated with a more intense inflammatory reaction in some organs.

scholarly journals Quantification of Leishmania infantumDNA in the bone marrow, lymph node and spleen of dogs

2013 ◽  
Vol 22 (3) ◽  
pp. 346-350 ◽  
Author(s):  
Rafael Antonio Nascimento Ramos ◽  
Carlos Alberto do Nascimento Ramos ◽  
Edna Michelly de Sá Santos ◽  
Flábio Ribeiro de Araújo ◽  
Gílcia Aparecida de Carvalho ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Real Time ◽  
Real Time Pcr ◽  
Biological Samples ◽  
Biological Sample ◽  
Clinical Signs ◽  
Parasite Load ◽  
Epidemiological Surveillance ◽  
Significant Difference

The aim of the present study was to quantify the parasite load ofLeishmania infantum in dogs using real-time PCR (qPCR). Bone marrow, lymph node and spleen samples were taken from 24 dogs serologically positive for L. infantum that had been put down by the official epidemiological surveillance service. According to the clinical signs the dogs were classified as asymptomatic or symptomatic. After DNA extraction, the samples were subjected to qPCR to detect and quantify L. infantum DNA. Out of the 24 dogs, 12.5% (3/24) were classified as asymptomatic and 87.5% (21/24) as symptomatic. Real-time PCR detected L. infantum DNA in all the animals, in at least one biological sample. In particular, 100% of bone marrow and lymph node scored positive, whereas in spleen, the presence of DNA was detected in 95.9% (23/24). In addition, out of 24 animals, 15 were microscopically positive to amastigote forms of L. infantum in bone marrow. No statistical significant difference was found in the overall mean quantity of DNA among the different biological samples (P = 0.518). Considering each organ separately, there was 100% positivity in bone marrow and lymph nodes, while among the spleen samples, 95.9% (23/24) were positive. Regarding the different clinical groups, the overall mean parasite load varied significantly (P = 0.022). According to the results obtained, it was not possible determine which biological sample was most suitable tissue for the diagnosis, based only on the parasite load. Therefore, other characteristics such as convenience and easily of obtaining samples should be taken into consideration.

scholarly journals Frequency of detection and load of amastigotes in the pancreas of Leishmania infantum-seropositive dogs: clinical signs and histological changes

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
William de Oliveira Kost ◽  
Sandro Antonio Pereira ◽  
Fabiano Borges Figueiredo ◽  
Artur Augusto Velho Mendes Junior ◽  
Maria de Fátima Madeira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Visceral Leishmaniasis ◽  
Body Condition ◽  
Leishmania Infantum ◽  
Clinical Signs ◽  
Low Frequency ◽  
Parasite Load ◽  
Cell Degeneration ◽  
Histological Changes ◽  
Etiological Agents

Abstract Background Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and is highly lethal in humans and dogs if left untreated. The frequency of this parasite and associated histological changes in the pancreas of dogs are poorly studied. Therefore, the objectives of this study were to evaluate the frequency of detection and load of amastigotes in the pancreas of L. infantum-seropositive dogs and to identify the clinical signs and histological changes associated with parasitism of this organ. Methods One hundred forty-three dogs from an endemic area in Brazil that tested seropositive for L. infantum were studied. The dogs were clinically examined, killed, and necropsied between 2013 and 2014. One fragment of the pancreas was randomly collected for histopathology and immunohistochemistry, and spleen and bone marrow were collected for culture. Results Leishmania amastigotes were detected in the pancreas of 22 dogs (15.4%) by immunohistochemistry, all exhibiting L. infantum parasitism in the spleen and/or bone marrow. Poor body condition and cachexia were only associated with infection of the pancreas with Leishmania spp. (p = 0.021) and were found in 40.9% of dogs with pancreatic infection. Anorexia, vomiting, and/or diarrhea were observed in 9.2% of dogs with pancreatitis. The median parasite load in the pancreas was 1.4 infected macrophages/mm2. Pancreatic histological changes and their frequencies were: granulomatous pancreatitis (28.0%), lymphoplasmacytic pancreatitis (23.8%), acinar cell degeneration (6.3%), fibrosis (5.6%), hemorrhage (2.1%), eosinophilic pancreatitis (0.7%), suppurative pancreatitis (0.7%), and necrosis (0.7%). Conclusions The present results demonstrate that L. infantum is one of the etiological agents of chronic pancreatitis in dogs; however, the frequency of detection and parasite load are low in this organ. The lack of an association of poor body condition and cachexia with pancreatitis and the low frequency of clinical signs commonly associated with pancreatitis suggest that a significant portion of the organ is not affected by this parasite. On the other hand, the association of poor body condition and cachexia with concomitant infection of the pancreas, spleen, and/or bone marrow with this parasite suggests that these manifestations are the result of a more advanced stage of canine visceral leishmaniasis. Graphic abstract

Correlations between tissue parasite load and common clinical signs in dogs naturally infected by Leishmania infantum

2021 ◽  
Vol 291 ◽  
pp. 109368
Author(s):  
Úrsula Maira Russo Chagas ◽  
Daniel Moreira de Avelar ◽  
Andreza Pain Marcelino ◽  
Gustavo Fontes Paz ◽  
Célia Maria Ferreira Gontijo
Keyword(s):  
Leishmania Infantum ◽  
Clinical Signs ◽  
Parasite Load

scholarly journals Pseudomonas aeruginosa las and rhl quorum-sensing systems are important for infection and inflammation in a rat prostatitis model

Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2612-2619 ◽  
Author(s):  
Lisa K. Nelson ◽  
Genevieve H. D'Amours ◽  
Kimberley M. Sproule-Willoughby ◽  
Douglas W. Morck ◽  
Howard Ceri
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Tissue Damage ◽  
Inflammatory Markers ◽  
Bacterial Colonization ◽  
Opportunistic Pathogen ◽  
Infection Model ◽  
Chronic Infections ◽  
Strain Pao1 ◽  
Rat Prostate

Pseudomonas aeruginosa frequently acts as an opportunistic pathogen of mucosal surfaces; yet, despite causing aggressive prostatitis in some men, its role as a pathogen in the prostate has not been investigated. Consequently, we developed a Ps. aeruginosa infection model in the rat prostate by instilling wild-type (WT) Ps. aeruginosa strain PAO1 into the rat prostate. It was found that Ps. aeruginosa produced acute and chronic infections in this mucosal tissue as determined by bacterial colonization, gross morphology, tissue damage and inflammatory markers. WT strain PAO1 and its isogenic mutant PAO-JP2, in which both the lasI and rhlI quorum-sensing signal systems have been silenced, were compared during both acute and chronic prostate infections. In acute infections, bacterial numbers and inflammatory markers were comparable between WT PA01 and PAO-JP2; however, considerably less tissue damage occurred in infections with PAO-JP2. Chronic infections with PAO-JP2 resulted in reduced bacterial colonization, tissue damage and inflammation as compared to WT PAO1 infections. Therefore, the quorum-sensing lasI and rhlI genes in Ps. aeruginosa affect acute prostate infections, but play a considerably more important role in maintaining chronic infections. We have thus developed a highly reproducible model for the study of Ps. aeruginosa virulence in the prostate.

scholarly journals CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS

1919 ◽  
Vol 30 (5) ◽  
pp. 455-481 ◽  
Author(s):  
Louise Pearce ◽  
Wade H. Brown
Keyword(s):  
Body Weight ◽  
Lethal Dose ◽  
Clinical Signs ◽  
Subcutaneous Administration ◽  
Signs And Symptoms ◽  
Chronic Infections ◽  
Duration Of Action ◽  
Small Doses ◽  
General Physical ◽  
Arsonic Acid

In the treatment of experimental trypanosomiasis of rabbits with subsequent appraisal of the value of the therapeutic agent used, there are certain experimental factors including uniform infecting strains of trypanosomes and the observation of general procedures of method and time of inoculation conditioned by the infection itself which must be taken into account. The conspicuous and characteristic clinical signs and symptoms seen in rabbit trypanosomiasis serve as criteria of the severity and duration of the disease, and it is obvious that the infection should be well established before treatment is instituted. For the same reason, before the question of a permanent cure can be established, treated rabbits should be kept under observation for a sufficient period of time, which with the species of organisms that we have used is at least 3 months. The therapeutic results with the amide of N-phenylglycine-p-arsonic acid were obtained in rabbits which showed well marked clinical signs of a definitely established disease, and in many instances the infection was extremely advanced and of prolonged duration. The five species which we have employed, Tr. brucei, Tr.gambiense, Tr. equinum, Tr. equiperdum, and Tr. evansi, are uniformly fatal in rabbits. With the usual acute, actively progressing infection of from I to 2 weeks duration produced by our strain of Tr. brucei, the drug has a curative range of from 0.2 to 0.35 gm. per kilo of body weight, when administered intravenously in single doses, or from one-third to one-half the minimal lethal dose. Of the twenty-nine rabbits treated with doses falling within this range, twenty-five, or 86 per cent, were permanently cured and there were no relapses observed with doses above 0.3 gm. The infection produced by our strain of Tr. gambiense is controlled by a slightly lower dose, since there were no relapses with single doses of 0.3 gm. and a single dose of 0.15 gm. effected a cure in one of three rabbits so treated. The therapeutic experiments with Tr. equinum, Tr. equiperdum, and Tr. evansi are too few to admit of final conclusions, but apparently from the evidence at hand, much the same curative range is operative in Tr. evansi infections, while larger doses or a different system of treatment should have been employed in the treatment of rabbits infected with our strains of Tr. equinum and Tr. equiperdum. In addition to the ultimate curative results obtained with single doses within the curative range, it is important to consider the marked therapeutic action with smaller single doses, as shown by the rapid regression and healing of the clinical lesions of the acute infections produced by all five species of trypanosomes together with a marked improvement in the general physical state of the animal. Moreover, large single doses, above those of the so called curative range, caused no disturbance of a toxic nature and were apparently well borne. A system of repeated dose therapy may be employed with advantage in the treatment of both initial and relapsed infections in rabbits, especially in those instances in which there is induration or even necrosis of tissues with weakness and emaciation of the animal host. The factor of time of repetition or the spacing of doses is in our experience as important as that of size of the dose employed and depends upon the rate, degree, and duration of action of the particular dose of the drug in question. Since the amide of N-phenylglycine-p-arsonic add apparently possesses the power of tissue penetration to a marked degree, it is desirable to give the second dose within a short time after the first in order that it may have a full opportunity for the immediate and complete development of its action. The repetition of small doses such as 0.15 gm. per kilo of body weight on successive or alternate days has given successful results as regards both the immediate regression and healing of lesions and ultimate permanent cures in severe, chronic infections. It is possible, however, to administer increasingly large doses, if this is necessary, since infected as well as normal rabbits exhibit a remarkable tolerance to repeated large doses of the drug. The therapeutic activity of small doses administered intramuscularly is quite comparable with that observed after similar doses given intravenously, as indicated by the rate of regression and healing of clinical lesions, while such effects proceed somewhat more slowly after subcutaneous injections. Permanent cures have been obtained in Tr. brucei infection with intramuscular and subcutaneous administration of single doses of from 0.2 to 0.5 gm. of the drug per kilo of body weight and in other instances with three repeated doses of 0.1 gm. per kilo given intramuscularly. One severely infected rabbit which received 0.75 gm. per kilo per os immediately following a small dose of sodium bicarbonate was also cured. The therapeutic experiments here reported represent only a portion of those carried out with N-phenylglycineamide-p-arsonic acid and the scope of the present paper does not permit a detailed description of the many phases of the experiments or a full discussion of the various factors involved and the results obtained, all of which we hope to publish at some future time.

Histopathologic lesions in conventional pigs experimentally infected with Haemophilus parasuis serovar 5

2015 ◽  
Vol 43 (02) ◽  
pp. 91-96 ◽  
Author(s):  
R.-L. Austin-Busse ◽  
A. Ladinig ◽  
G. Balka ◽  
S. Zoels ◽  
M. Ritzmann ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Control Group ◽  
Post Inoculation ◽  
Haemophilus Parasuis ◽  
Tissue Samples ◽  
Group A ◽  
Pathologic Lesions ◽  
Group B ◽  
Kidney Lesions ◽  
Challenge Group

Summary Objective: In the present study various tissues of pigs were investigated for the presence of histopathologic lesions after an experimental infection with Haemophilus (H.) parasuis serovar 5. Material and methods: Conventional pigs (n = 36) were divided into a control group B (n = 9) and a challenge group A (n = 27), which was infected intratracheally. Pigs that did not die prior to study termination were euthanized on day 14 post inoculation. Postmortem samples of the lung, heart, liver, kidney, spleen, left tarsal joint capsule and brain were collected. Results: All but one pig with detectable histopathologic lesions (n = 11) showed typical macroscopic changes. Histopatho logic examination of all tissue samples identified pyelitis (n = 10), synovitis (n = 7) and meningitis (n = 7) and all those animals were euthanized prior to study termination. No histopathologic lesions were found in pigs of the control group. The correlations between pyelitis and meningitis, pyelitis and synovitis and synovitis and meningitis were significant (p < 0.001). No significant correlation could be observed between the histopathologic and the clinical examination of the joints. The investigation of samples from the joints by PCR was not significantly correlated with the observed synovitis. The clinical observation of neurologic signs was significantly correlated with meningitis (p = 0.03). A significant correlation (p < 0.001) could be detected between meningitis and the detection of H. parasuis by PCR in brain samples. Conclusions: H. parasuis constantly causes clinical signs and pathologic lesions as soon as it infects the brain while it can infect the joints without causing histopathologic lesions. Pigs with histopathologic lesions do not always show typical clinical signs. Only few studies described the finding of kidney lesions in pigs with Glässer’s disease and this is the first study to describe a pyelitis in pigs experimentally infected with H. parasuis. The observed pyelitis mainly occurred in acute cases.

scholarly journals Osteopetro-Rickets: A Rare Paradoxical Association in an Infant

2012 ◽  
Vol 32 (1) ◽  
pp. 88-89
Author(s):  
MB Patil
Keyword(s):  
Case Report ◽  
Key Words ◽  
Bone Disease ◽  
Clinical Signs ◽  
Severe Anaemia ◽  
Management Options ◽  
Positive Balance ◽  
Malignant Osteopetrosis ◽  
Infantile Malignant Osteopetrosis ◽  
Key Words Osteopetrosis

Infantile malignant osteopetrosis is a hereditary bone disease with intense positive balance of body calcium. Osteopetro-rickets is a very rare paradoxical association of infantile osteopetrosis and rickets. This is a case report of an infant with osteopetro- rickets. He presented with severe anaemia, splenomegaly, hepatomegaly and clinical signs of rickets. The clinical, biochemical and skeletal survey showed osteopetrosis and rickets. We also describe the pathophysiologic mechanism and various management options. Key words: Osteopetrosis; Osteopetro-rickets; Rickets DOI: http://dx.doi.org/10.3126/jnps.v32i1.5292 J. Nepal Paediatr. Soc. Vol.32(1) 2012 88-89

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