Keywords : Rabbits

Comparative efficacy of platelet-rich plasma and dextrose prolotherapy for stifle joint arthritis in a rabbit model

Fawad Khalil; Hamid Akbar; Muhammad A. Hayat; Hamad B. Rasheed; Sadaf Aslam; Ayesha Safdar; Fiaz Ahmad; Hafiz M. Ahmad; Muhammad T. Sajjad

Iraqi Journal of Veterinary Sciences, 2023, Volume 37, Issue 2, Pages 531-536
DOI: 10.33899/ijvs.2022.133730.2285

This study aimed to investigate the efficacy of PRP and dextrose PRL in stifle joint arthritis in rabbits.Sixteen healthy adult male rabbits were allocated into groups A (n=8) and B (n=8). After induction of arthritis in all experimental animals, the animals of group A were treated with intra-articular injection of PRP, while the animals of group B were treated with dextrose PRL. Pain scoring was evaluated by the Simple Descriptive Pain scale at 0d, 6d, 13d, and 19d, while radiographic scoring was examined by Kellgren and Lawrence grading system at pre-induction, post-induction, and post-treatment. The hematological parameters, including PLT, HB, WBC, PCV, RBC, monocytes, and lymphocytes, were assessed in blood samples at 0d, 6d, 13d, and 19d. We observed that Pain scoring showed a significantly lower (P<0.05) value in group A than in group B at 13d and 19d. Radiographic scoring was significantly lower (P<0.05) in group A than the group B during post-treatment. However, during the pre- and post-monoiodoacetate (MIA) induction, there was no significant difference (P>0.05) in radiographic scoring between both groups. The PLT concentration was increased, and monocyte was decreased in the group A animals than the group B animals at 13d and 19d (P<0.05), while WBC, RBC, PCV, HB, and lymphocyte concentration showed no significant difference (P>0.05) between both groups. In conclusion, the application of PRP is an effective method for treating stifle joint arthritis compared to the dextrose PRL in the rabbit model.

The amelioration of vitamin E on histological changes of rabbit’s brain treated with zinc oxide nanoparticles

Atheer N. Taha; Hana Kh. Ismail

Iraqi Journal of Veterinary Sciences, 2023, Volume 37, Issue 1, Pages 95-104
DOI: 10.33899/ijvs.2022.133599.2265

Zinc-oxide in nanoparticles is suggested to be one of the crucial nanoparticles due to its expanse implementation in many industries, like electrons, food supplements, and maquillage and makeup. This led to more individual exposure to ZnO NPs through inspiration and skin penetration. This study objected to estimating the toxic impact of ZnO NPs on the cerebral cortex, hippocampus, and cerebellum in male rabbits by studying the gross and histological changes. Twenty-four adult male rabbits were divided randomly into four groups, comprising six animals. The first group was considered as the control group left without treatment; the second group was treated with 100 mg/kg BW of vitamin e orally, the third group was treated intraperitoneally with ZnO NPs 600 mg/kg BW, and the fourth group was treated with I/P 600 mg/kg BW of ZnO NPs in addition to 100 mg/kg BW orally of vitamin e twice weekly for twenty-one days. The histological results showed degenerative, necrotic changes in neurons with a vascular and inflammatory response in the cerebral cortex, hippocampus, and cerebellum in the second group of rabbits treated with ZnO NPs. In contrast, the treated rabbits with ZnO NPs and vitamin E revealed slight improvement in the histological picture of brain sections. Also, there was an alteration in acetylcholine levels in all groups compared with the control group.

The impact of nano zinc oxide particles on the histology of the male reproductive system of adult male rabbits

Atheer N. Taha; Hana Kh. Ismail

Iraqi Journal of Veterinary Sciences, 2023, Volume 37, Issue 1, Pages 105-113
DOI: 10.33899/ijvs.2022.133632.2270

The goal of our research is to evaluate the histological impact of nano ZnO particles (NZnO) on the testis and epididymis of adult male rabbits treated with I.P of 600mg/kg body weight of nano ZnO particles twice a week for three weeks and to the protective effect of vitamin E versus the effect of nano zinc oxide particles. Twenty-four adult male rabbits were used in this research and divided into four groups. The first group was the control group injected with intraperitoneal distal water, and the second group was injected with 600mg/kg body weight of nano Zno particles I.P. twice a week for three weeks, the third group was injected with 600 mg/kg body weight of nano Zno particles I.P. and co-administrated with 100 mg/kg body weight of vitamin e orally, while the fourth group received 100mg/kg body weight of vitamin e orally. The histological results showed that the nano ZnO particles treatment causes noticeable changes in the testis and epididymis. These changes are characterized by thickening of tunica albuginea of testis, degenerative and necrotic changes of germ cells lining the seminiferous tubules, arrest of spermatogenesis, giant cell formation, degeneration, and necrosis of epithelial cells lining epididymis canals. The canals are free from sperms is observed. As for the group of animals treated with nano ZnO particles co-administrated with vitamin e showed improvement in the histological changes compared with the control and group treated with vitamin e only showed normal architecture of testis and epididymis. Moreover, there is a decrease in the level concentration of Testosterone of the animals treated with nano ZnO particles compared with other groups.

Experimental study of the effect of Plantago major leaves extract on contaminated excisional wound healing in rabbits

Mustafa M. Mahmood; Areeg K. Mahdi

Iraqi Journal of Veterinary Sciences, 2022, Volume 36, Issue Supplement I, Pages 31-39
DOI: 10.33899/ijvs.2022.134991.2432

The current study was performed to estimate the influence of topical application of 10% of Plantago major leaves extract (PMLE) on a healing process of contaminated excisional wound in local breed rabbits. Twenty adult local breed male rabbits were used. After the animals have generally anesthetized, two 2×2 cm full thickness wounds were created in thoracic region on right and left side (1wound/side) for each animal. Wounds on right side of animal were treated by topical irrigation with normal saline/daily, this consider as control (group A). While, left side wounds were treated by topical application of 10% PMLE ointment (once/day) that consider as treated (group B) dressing was used after each treatment for both groups. Wound healing was evaluated through macroscopic examination, wound contraction rate (WCR) assessment and histopathological examination. Results of macroscopic examination confirmed that PMLE has a role in acceleration healing when compared to control group. These outcomes were parallel with WCR results in which reflect the mean rate of wound contraction on days 7th, 14th, and 21st ‎in PMLE-treated group was ‎significantly higher (P<0.001) than that of ‎the normal saline-treated group. Histopathological examination results confirmed early increased in new blood vessels formation, fibroblasts proliferation, marked collagen precipitation and early epithelization in group PMLE compared to group A. This study confirmed that topical application of 10% of PMLE (once/a day) has an effective role in accelerate contaminated wound healing through its phenolic and flavonoid contents as recorded by high performance liquid chromatography (HPLC) assessment that act as antioxidant and anti-inflammatory substance which help in the enhancement the WCR through encourage early and additional fibroblast proliferation and angiogenesis when compared to control group.

The histologic effects of high doses of botulinum toxin a on the rabbit's salivary gland

Luma I. Khalel; Jawnaa Khalid Mammdoh; Abdullah A. Ahmed

Iraqi Journal of Veterinary Sciences, 2022, Volume 36, Issue 4, Pages 1111-1117
DOI: 10.33899/ijvs.2022.133149.2184

The exact mechanism of botulinum toxin A (BTX-A) on submandibular salivary gland (SMG) regarding its function and histology remains unclear. The goal of this work is to clarify the histological effects of BTX-A (at high doses) in SMG in rabbits after one week. Thirty adult male rabbits were used in this study and they arranged as group 1 includes rabbits which received any treatment and kept for one week duration. Group 2 includes rabbits which received 8 units of BTX-A. Group 3 includes rabbits which received 16 units of BTX-A. Animals were euthanized with ether after one week. Specimens of SMG from all rabbits were taken to perform a routine histological preparation and examination. Sections of rabbits of group 2 and group 3 showed evidence of edema that is surrounding striated ducts, congested blood vessels, and even necrosis of both serous and mucous acini. Some sections exhibited features of degeneration of mucous acini. Hemorrhage was noticed in some sections. Injection of either 8 or 16 units of BTX-A induces several alterations in the submandibular glands’ histology.

Expression of Ki67 in submandibular salivary glands of rabbits after BTX injection: Histological and immunohistochemical study

Abdullah A. Ahmed; Jawnaa K. Mammdoh

Iraqi Journal of Veterinary Sciences, 2022, Volume 36, Issue 3, Pages 611-620
DOI: 10.33899/ijvs.2021.131101.1919

This study aimed to examine the possible histological effects of local injections of BTX in rabbits submandibular SGs and to find the dose-dependent and time relationship between injections and study immunohistochemistry expression of Ki67. Thirty male rabbits randomly divided into 3 groups (10 rabbits for Each) 1st group: control (without treatment), 2nd group treated with 5U of BTX and 3rd group treated with 10U of BTX, five animals of each group were sacrificed in 1st week of treatment and another five animals sacrificed in 4th week of treatment. The rabbit was anesthetized then injected with the BTX in the gland. The histopathological changes in Group 5, 10 Unit BTX (1st week) were vacuolar degeneration of mucous acini cells, degeneration of serous acini cells, while the lesions showed hyperplasia and necrosis of epithelial cells lining striated ducts, necrosis of serous acini epithelium. The Diameter of mucous acini were found to be significantly increased in 10 Unit BTX groups. During the 1st and 4th weeks, the surface area of the striated ducts in the 5- and 10-unit BTX groups increased significantly, and the number of striated ducts in the 10 Unit BTX group decreased significantly when compared to the 1st week period of the same group. BTX groups revealed moderate to weak positive cytoplasmic reactivity for Ki67 protein in the parenchymal tissue of the glands. We conclude that BTX causes histological changes in the salivary gland as well as affecting Ki67. This data could be used in a future study to investigate the usage of BTX in cancer treatment.

A Comparison between ketamine-xylazine and ketamine-midazolam or all of them to induce balance anesthesia in rabbits

Mahmood B. Mahmood

Iraqi Journal of Veterinary Sciences, 2022, Volume 36, Issue 2, Pages 499-506
DOI: 10.33899/ijvs.2021.130618.1852

The objective of this projectwas to study the induction of smooth anesthesia characterized by good induction (hypnosis), analgesia and good recovery with mild side effects caused by drugs. The effect of using Ketamine with both xylazine and midazolam KXM was investigated in adult rabbitsand compared with the positive control group that was administered with ketamine alone K at 40 mg/kg i.m, and with ketamine - xylazine group KX at 40 and 4 mg/kg i.m respectively, and with ketamine - midazolam group KM also at 40 and 4 mg/kg i.m respectively. Administration of xylazine and midazolam each one alone at 4 and 2 mg/kg I.M induced analgesia in a dose-dependent manner through a significant elevation of the electrical voltage after injection when compared with its value before injection. A minimum doses of a mixture KXM at 20,2 and 2 mg/kg i.m respectively, induced good hypnosis with rapid induction and long duration with recovery periods without significant variations in vital physiological parameters (respiratory rate, heart rate, and rectal temperature) and some biochemical parameters (GPT and GOT and glucose level) comparing with groups K, KX and KM. The outcomes of this work were revealed to the induction of proficient general anesthesia that was described by effective hypnosis with analgesic efficacy throughout the administration a minimum doses of ketamine/xylazine/midazolam combination in rabbits.

Efficacy of Urtiea dicica extract for amelioration of brain lesions induced by ethylene glycol in male rabbits

Ahmed M.A. Alsaidya; Hana Kh. Ismail; Enas S. Mostafa

Iraqi Journal of Veterinary Sciences, 2022, Volume 36, Issue 2, Pages 485-488
DOI: 10.33899/ijvs.2021.130563.1848

The nervous system is the most delicate organ to neurotoxic substances that affects the development of neurochemicals, including neurotransmitters, and organization of ion channels. Urtica dioica (Nettle) is one of the medicinal plants, which has been increasingly highlighted used for its anti-inflammatory and anti-oxidative components. This study aimed to evaluate the improvement effects of Urtica dioica extract on the histopathological lesions of nervous system in rabbit model. Fifteen male rabbits of 700-800 grams separated into three groups, the first group is the control, and the second group were treated with 0.75% ethylene glycol (EG) in water for 30 days, group three were combination treated group with both EG and Urtica dioica at 100 mg/kg for 10 days. Microscopic histological examination discovered generalized congestion of blood vessels at the cerebrum and cerebellum, degeneration and necrosis of the neuronal cells of the cerebral cortex which characterized by swelling of the degenerative cells, while necrotic cells characterized by shrunken and pyknosis of the cells in the cerebellum cortex presents of inflammatory cells in the meninges. In conclusion, the histopathological examination of brain sections of rabbits treated with ethylene glycol in addition to Urtica dioica extract showed slight improvement in the histological pictures of the cerebellum and cerebrum.

Protective effect of Urtica dioica in liver and kidney damages induce by ethylene glycol in rabbits: A histopathological study

Muataz A. Al-Akash; Haitham A. Rajab; Ibtisam N. Al-Assaf

Iraqi Journal of Veterinary Sciences, 2022, Volume 36, Issue 1, Pages 167-170
DOI: 10.33899/ijvs.2021.129606.1666

Urtica dioica is used in the many countries as seasoning and as an herbal medicine (antioxidant). In this study, adult male locale rabbit was separated into five groups, Group 1 considered as control, Group 2 to 5 animals were treated with 0.75% ethylene glycol (EG) in water to induce renal and liver damage till 30th day. The group 3 to 5 animals were feed extract of the plant of U. dioica at a dosage of 100 mg/kg body weight from day 15 to the day 30. The extracts were administered twice daily orally. Liver histopathological changes characterized by vacuolar degeneration and coagulative necrosis of hepatocytes, congestion and dilatation of central vein and sinusoids. Renal histopathological changes characterized by deposition of oxalates, blood vessels congestion infiltration of inflammatory cells and change in renal glomeruli in GE treated groups. While histopathological changes in the animals group treated with U. dioica extract and ethylene glycol showed an increase improvement of the histological features of liver tissue, were limited dilatation of renal tubules with less deposition of oxalates, as well as slight infiltration of inflammatory cells in the interstitial tissue. Finally, as a conclusion we noticed that U. dioica extracts had the ameliorative effect of ethylene glycol-induced hepatic and renal histopathological.

A Comparative pharmacological study on moxidectin and propolis ointment in rabbits naturally infested with Psoroptes cuniculi

Mohamed F. Dakroury; Asmaa A. Darwish

Iraqi Journal of Veterinary Sciences, 2021, Volume 35, Issue 4, Pages 725-731
DOI: 10.33899/ijvs.2021.128171.1560

Ear mange is an annoying problem for all animal breeders including rabbit's breeders. This study aimed to compare the efficacy of moxidectin and 10% propolis ointment on rabbits infested with Psoroptes cuniculi with especial reference to some related biochemical parameters diagnostic and prognostic value. For this purpose, a total of thirty-two rabbits: 8 non-infested rabbits (control group (CG) and 24 naturally infested rabbits were used. Infested rabbits were equally divided into three groups: 1st group remained without treatment (diseased group (DG)), 2nd group was treated with moxidectin ((0.2 mg/kg body weight) S/C (MG)). Propolis ointment (10%) was applied topically to rabbits of the 3rd group (PG) once daily. Ear scrapes and blood samples were taken on 0, 7, 14 and 21 days. The ear scraping was examined microscopically and the biochemical parameters were estimated and statistically analyzed. The results cleared that moxidectin achieved the complete healing (14th day) faster than propolis ointment (21st day), but MG suffered from a significant (P<0.05) hypoalbuminemia, increased liver and kidney function tests and cortisol levels when compared to PG. Liver and kidney function tests and cortisol yielded good values of the area under the curve, sensitivity%, specificity%, likelihood ratio, PPV%, NPV%, accuracy rate% in DG, MG (except creatinine) and PG. The study concluded that propolis had a prominent antipsoroptic effect without inducing hepatic or renal toxicity. Liver and kidney function tests and cortisol may be useful markers for rabbit mange diagnosis and prognosis and following up its treatment. 

Structural study of uterine tubes of the rabbit (Oryctolagus cuniculus) at different postnatal periods

Faeq Jabar Al-Saffar; Massarat Almayahi

Iraqi Journal of Veterinary Sciences, 2019, Volume 33, Issue 2, Pages 277-288
DOI: 10.33899/ijvs.2019.162911

This study was designed to investigate the histomorphological changes in the uterine tubes of the local rabbits during three different periods of ages that were kitten, immature and mature stages of life. For such study, twenty-four female rabbits were used. Procedure of routine histological technique was performed to prepare histological sections by using general and special histochemical stains. Gross findings revealed the presence of bilateral uterine tubes which comprised thick short coiled preampulla, thin long ampulla and the isthmus which was shortest and straight region joined to the uterus. Microscopically three regions were identified according to the differences in their histological characteristic features. Data revealed that the wall of uterine tubes in kittens was not fully developed, whereas in immature does, global histological and histochemical changes were identified compared to kittens while mature does indicated critical role of the post weaning period on the development of the animals. Changes were specially recognized by histochemical procedure which showed strong positive reactions especially isthmus which obviously reacted with PAS, Ab, combined PAS-AB. In conclusion, current data showed unique differences of the uterine tubes in the local rabbits compared to other mammals especially those of rodentia species.

Comparative pharmacokinetic study of theaflavin in healthy and experimentally induced liver damage rabbits

Sarhan Rashid

Iraqi Journal of Veterinary Sciences, 2019, Volume 33, Issue 2, Pages 235-242
DOI: 10.33899/ijvs.2019.162962

This current work aimed to study the pharmacokinetics of theaflavin in healthy and hepatotoxic rabbits for comparison. Aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were significantly raised (P<0.05) after administration of 0.2 mg/kg body weight (BW) Carbone tetrachloride (CCL4) subcutaneously. Pharmacokinetic parameters calculated following administration of theaflavin intravenously and orally at 30 mg/kg and 500 mg/kg respectively to both healthy animals and those with damaged liver. Theaflavin concentration in blood measured by HLPC at various time intervals. Pharmacokinetic results showed that theaflavin concentration when given orally reached its maximum concentration after 5 hours in healthy rabbits. While in hepatotoxic group, theaflavin concentration achieved the highest level in blood after three hours. Theaflavin bioavailability in hepatotoxic animals was significantly high and almost double its bioavailability in healthy animals. Results revealed that the area under curve (AUC) value in rabbits with damaged liver was significantly greater than in healthy group (P<0.05). t ½ of theaflavin after intravenous administration was 6.3±0.82 hour in damaged liver group which is significantly higher than that in healthy group (P<0.05). Theaflavin mean concentration in hepatotoxic group required more than 3 hours to decline to 352±19.4 ng/ml when compared to its concentration in healthy group which is required only 45 minutes to decrease to 310± 9.5 ng/ml. In conclusion liver has critical impact on the pharmacokinetics of theaflavin especially bioavailability and biotransformation and this research recorded reasonably large differences between healthy and liver damaged groups regarding theaflavin pharmacokinetic parameters which may result in negative influences on its biological efficacy when used in the treatment of various diseases.

Study of histopathological and biochemical effect of Punica granatum L. extract on streptozotocin -induced diabetes in rabbits

E.R. Sarhat; S. A. Wadi; B.I. Sedeeq; Th. R. Sarhat; N.A. Jasim

Iraqi Journal of Veterinary Sciences, 2019, Volume 33, Issue 2, Pages 189-194
DOI: 10.33899/ijvs.2019.125523.1045

This study was undertaken to determine the antidiabetic effects of oral administration of Punica granatum L. extract on serum and tissues of streptozotocin induced diabetic rabbits at 100 mg/kg. The present study was carried out at the Faculty of veterinary Medicine, Tikrit University, from February to August 2017 for 10 weeks. For this purpose, 30 rabbits were randomly separated into three groups, each containing 10 animals: Group 1, healthy control rabbits; Group 2, diabetic rabbits received streptozotocin (STZ, 65 mg/kg); Group 3, diabetic rabbits treated with PS extract (the 100 mg PS+1 ml DW) for 21 days. At the end of experiment, blood samples were taken for measuring serum biochemical parameters. For histopathological evaluation, sections of kidneys were fixed in 10% buffered formalin and 5micron thick sections with H&E stain were prepared using routine histopathological techniques. The treatment revealed that PSE extract significant decreased serum glucose throm-bospondin-1, nitric oxide, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase alkaline phosphatase, and C-reactive protein in diabetic treated rabbits as compared to diabetic rabbits. Histopathology of kidney showed lesions similar to human glomeruloscleroses, glomerular membrane thickening, arteriolar hyalinization and tubular necrosis. From the above one can conclude that PSE extract possess nephroprotective effect in experimentally induced diabetic rabbits.

A comparative study between kessler suture versus polypropylene mesh implantation to repair tenotomized common calcaneal tendon in rabbits

Saddam Humadi

Iraqi Journal of Veterinary Sciences, 2019, Volume 33, Issue 2, Pages 289-296
DOI: 10.33899/ijvs.2019.162907

The present study is assigned to throw the light on the benefit of using Kessler suture compared with polypropylene mesh implantation in healing of induced tenotomy of common calcaneal tendon in a rabbit model based on clinico-histopathological evaluation. Twenty adults New Zealand white male rabbits were used for this clinical prospective study divided equally and randomly into two groups. The first group, (suture group n=10) and the second group (mesh group n=10). Under the effect of general anesthesia, longitudinal skin incision over the common calcaneal tendon was made, and the skin flap was reflected. The tendon was isolated by blunt dissection from the surrounding tissue, with small curved forceps. Simulation of a rabbit’s common calcaneal tendon rupture was made by sharp transvers incision with scalpel. The first group repair with (Kessler Suture) using polypropylene suture size 4.0. In contrast, the second group repair with (polypropylene mesh implantation) after initial suturing of the cut ends of tendon by two simple interrupted stitches using polyglyconate suture size 4.0. The surgical skin wounds were re-stitched by simple interrupted pattern with 3-0 silk. After clinical follow-up of the treatment rabbits, certain secondary health problems were encountered represented by swelling of operative site and lameness. Grossly, adhesions were noticed between the tendon and subcutaneous tissue in rabbits of both groups. Microscopical examination reflected presence of inflammatory cells perivascular edema and few capillaries at two months. At the end of experiment there were perfect orientation and organization of collagen fibers in mesh group in comparing with suture group. Based on the results obtain from this study, it seemed that both groups reflected best outcome in healing of operated tendons with superiority of mesh group in comparing with suture group.

The first unequivocal report of Encephalitozoon cuniculi in rabbits and Encephalitozoon intestinalis in cattle in Mosul city-Iraq

Saevan Saad Al-Mahmood; Hafidh I. Al-Sadi

Iraqi Journal of Veterinary Sciences, 2015, Volume 29, Issue 1, Pages 19-26
DOI: 10.33899/ijvs.2015.116859

The aim of present study was to report spontaneous Encephalitozoon cuniculi (E. cuniculi) infection in rabbits and Encephalitozoon intestinalis (E. intestinalis) infection in cattle in Mosul city - Iraq. Fecal samples were collected randomly from 142 rabbits and 115 cattle during the period from June, 2012 to June, 2013. Thin smears were prepared from the fecal samples and stained with different fecal stains, as well as the indirect immunofluorescent antibody technique. Infected rabbits were necropsied and pathology of the infection was described. The result showed that microsporidiosis was detected in 41 (26.9%) rabbits and in 12 (10.4%) cattle. E. cuniculi spores were identified in 31 out of the 41 rabbits (73.2%) and E. intestinalis in 7 out of the 12 cattle (58.3%). Infected rabbits showed vasculitis, granulomatous encephalitis, chronic interstitial nephritis, granulomatous hepatitis, cholangitis, vasculitis and non – suppurative pneumonia, infiltration of mononuclear cells in most layers of the intestines, and hyperplasia of lymphoid tissues. E. cuniculi spores were seen in the liver, kidneys and lungs. This study considered the first one that report microsporidiosis (E. cuniculi, E. intestinalis) in Mosul city - Iraq.

Pathological findings associated with experimental Mycobaterium bovis infection in rabbits

Khalel H. Al-Joboury

Iraqi Journal of Veterinary Sciences, 2005, Volume 19, Issue 1, Pages 83-89
DOI: 10.33899/ijvs.2005.37424

During the 2nd week post inoculation of thirteen rabbits with Mycobacterium bovis tuberculosis lesions appeared in the lungs, liver, spleen, kidney, mediastinal and hepatic lymph nodes and in the omentum with an equal distribution in these organs. During the 4th week post inoculation, these tuberculosis lesions increased in size to become well developed granulomas with caseated centers. These granulomas persisted to the 6th, 8th and 10th weeks post inoculation and became more encapsulated later on. Three rabbits died during the 7th week post inoculation due to generalized tuberculosis.