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Introduction: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs., Methods: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation., Results: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy., Conclusion: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment., (© 2024 S. Karger AG, Basel.)

Objective: To summarize the pathological characteristics of medication-related osteonecrosis of the jaw (MRONJ) specimens after jaw curettage or jaw osteotomy treatment and to comprehensively analyze the relationship between the different pathological features, treatment methods, and treatment effects to provide new ideas for effective treatment of MRONJ in clinical work., Methods: The clinical and pathological data were collected from 23 patients with MRONJ who were treated with curettage (18 patients) and jaw osteotomy (5 patients) at the Department of Oral and Maxillofacial Surgery of Peking University Hospital of Stomatology between June 2014 and December 2015. The pathological characteristics of MRONJ were summarized and analyzed with treatment effects based on various surgical treatment methods. The diagnostic criteria and disease staging of MRONJ were determined according to the 2014 American Association of Oral and Maxillofacial Surgeon's Position Paper., Results: In this study, 5 patients have treated with jaw segmental osteotomy, and all of them were in stage Ⅲ; the other 18 patients were treated with jaw curettage, including 5 patients in stage Ⅱ and 13 patients in stage Ⅲ. The pathological features of MRONJ in five cases of jaw segmental osteotomy were divided into three adjacent regions from shallow to deep: inflammation region (IR), sclerosis region (SR), and bone remodeling layer (BRL). Moreover, three types of pathological features of specimens from traditional curettage were defined as type 1 (IR), type 2 (IR + SR), and type 3 (IR + SR + BRL). The pathological features of the patients treated with jaw curettage were: type Ⅰ, 38.9% (7/18); type Ⅱ, 44.4% (8/18); type Ⅲ, 16.7% (3/18). Complete healing was achieved in 5 patients treated with jaw segmental osteo-tomy. Moreover, 2 cases with type Ⅰ, 1 case with type Ⅱ, and 1 with type Ⅲ completely healed after jaw curettage, while 5 cases with type Ⅰ, 7 cases with type Ⅱ, and 2 cases with type Ⅲ experienced recurrence after surgery., Conclusion: Pathological features of continuous regions of inflammation, sclerosis, and bone remodeling layer were identified from shallow to deep, based on the microscopic observation of jaw segmental osteotomy samples. Insufficient removal of the sclerotic region during jaw curettage that blocks the required blood, nutritional factors, and mesenchymal stem cells seems to be a common cause for failed treatment of MRONJ after curettage surgery.

Background: Focal segmental glomerulosclerosis (FSGS) is characterized by podocyte damage and severe proteinuria. The exact mechanism of podocyte damage and loss remains unclear. Necroptosis, a lytic form of programmed cell death mediated by RIP3 and MLKL, has emerged as an important cell death pattern in multiple tissues and cell types. Necroptosis in FSGS has not been investigated., Methods: Public GEO data regarding podocyte treated with vehicle or adriamycin (ADR) was identified and analyzed. Cultured human podocytes were used to explore the activation of necroptosis upon ADR stimulation. The expression of necroptosis pathway molecules, p-RIP3 and p-MLKL, was examined in the glomeruli and defoliated urinary podocytes of patients with FSGS. The effect of necroptosis inhibition was assessed in ADR-induced glomerulopathy mice using GSK872., Results: Publicly available RNA-sequencing data analysis showed that both necroptosis and NLRP3 inflammasome pathway were up-regulated in ADR-injured podocyte. Immunofluorescent staining showed increased expression of p-RIP3 and p-MLKL, the active forms of RIP3 and MLKL, in podocytes of FSGS patients and ADR-induced glomerulopathy mice but not in the normal control. GSK872, an RIP3 kinase inhibitor, significantly inhibited the expression of p-RIP3, p-MLKL and activation of NLRP3 in cultured podocytes treated with ADR. GSK872 treatment of mice with ADR-induced nephropathy resulted in the reduced expression of p-RIP3, p-MLKL, NLRP3 and caspase-1 p20. GSK872 also significantly inhibited the expression of p-MLKL in the podocytes of ADR-induced nephropathy, resulting in the attenuation of proteinuria and renal histological lesions., Conclusion: Necroptosis pathway might be a valuable target for the treatment of FSGS., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Purpose: The study was conducted to evaluate efficacy of intracameral lidocaine hydrochloride 1% and tropicamide injection 0.02% for anaesthesia and mydriasis in manual small-incision cataract surgery (MSICS) and to report any adverse drug reaction., Methods: This was a randomized, prospective, observational study on 32 participants that took place from October 2021 to March 2022 (6 months). Patients between age group 40-75 year with nuclear sclerosis cataract and pupil diameter >6 mm in preoperative evaluation were included in the study. Patients with pseudoexfoliation, rigid pupil, senile miosis, history of uveitis, ocular trauma, recent ocular infections, with known allergy to tropicamide, all types of glaucoma were excluded from the study., Results: Thirty-two eyes with nuclear sclerosis cataract who underwent MSICS were studied. Fixed dose combination of 2 ml phenyl epinephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) intracamerally was used for mydriasis and analgesia. More than 7 mm pupillary dilatation was achieved within 20 seconds of injection in 29 cases (90.6%). Mild pain and discomfort was noted in 12 cases (37.5%). Postoperative day 1 unaided visual acuity was in the range of 6/18-6/12 for all patients and grade 1 iritis was seen in 7 cases (21.8%) which was self-limiting. No adverse event like corneal decompensation or TASS were noted., Conclusion: Thus, Intracameral injection of mydriatic provides rapid and sustainable mydriasis and analgesia for manual SICS., Competing Interests: None

Background: Breast augmentation with polyacrylamide gel (PAAG) injection was approved in China in 1998 and later banned in 2006. The ban ensued numerous complaints from patients such as pain, induration, deformation, infection, displacement, and milk deposition associated with PAAG injection. To date, no study has investigated the long-term effect of PAAG migration on autoimmune diseases., Case Presentation: We report a rare case of a 49-year-old female patient with familial vitiligo who receiving PAAG injection for breast augmentation. The patient reported to have felt persistent movement of PAAG in her thoracoabdominal area for almost 20 years. Furthermore, the PAAG-induced chronic inflammation that aggravated vitiligo, which in turn promoted skin sclerosis. This damaged the breast contracture, increased chest tightness and induced mild breathing problems., Conclusion: Here, we present a rare case in which a patient with a family history of vitiligo experienced long-term complications after receiving PAAG injection for breast augmentation. This case highlights the relationship between vitiligo, migration of PAAG and tissue hardening and skin contraction., Level of Evidence: Level V.

Objective: Patients with epilepsy often ask if recurrent seizures harm their brain and aggravate their epileptic condition. This crucial question has not been specifically addressed by dedicated experiments. We analyze here if intense bilateral seizure activity induced by local injection of kainic acid (KA) in the right hippocampus produces brain damage in the left hippocampus., Methods: Adult guinea pigs were bilaterally implanted with hippocampal electrodes for continuous video-electroencephalography (EEG) monitoring. Unilateral injection of 1 μg KA in the dorsal CA1 area induced nonconvulsive status epilepticus (ncSE) characterized by bilateral hippocampal seizure discharges. This treatment resulted in selective unilateral sclerosis of the KA-injected hippocampus. Three days after KA injection, the animals were killed, and the brains were submitted to ex vivo magnetic resonance imaging (MRI) and were processed for immunohistochemical analysis., Results: During ncSE, epileptiform activity was recorded for 27.6 ± 19.1 hours in both the KA-injected and contralateral hippocampi. Enhanced T1-weighted MR signal due to gadolinium deposition, mean diffusivity reduction, neuronal loss, gliosis, and blood-brain barrier permeability changes was observed exclusively in the KA-injected hippocampus. Despite the presence of a clear unilateral hippocampal sclerosis at the site of KA injection, no structural alterations were detected by MR and immunostaining analysis performed in the hippocampus contralateral to KA injection 3 days and 2 months after ncSE induction. Fluoro-Jade and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining at the same time points confirmed the absence of degenerating cells in the hippocampi contralateral to KA injection., Significance: We demonstrate that intense epileptiform activity during ncSE does not cause obvious brain damage in the hippocampus contralateral to unilateral hippocampal KA injection. These findings argue against the hypothesis that epileptiform activity per se contributes to focal brain injury in previously undamaged cortical regions., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Purpose: To evaluate the morphological effects of injected sclerosing agents into the liver., Methods: This study was performed on twenty dogs, distributed into five groups: Group 1 (n = 5) - control, Group 2 (n = 5) - injection of 50% glucose solution inside hepatic parenchyma and animals followed during seven days, Group 3 (n = 10) - injection of ethanol inside hepatic parenchyma and animals distribution into two subgroups Subgroup 3A (n = 5) - followed during 24 hours and subgroup 3B (n = 5) - followed during seven days (group 3B), Group 4 (n = 5) - ethanol injection inside left portal vein branch and followed during 24 hours. Livers were macroscopically evaluated, submitted to hepatic arteriography and portography, then histology., Results: All animals in Group 4 died within 23 hours due to diffuse hepatic necrosis. The animals of groups 2 and 3 had a satisfactory evolution. Fibrosis formed in the segment reached by the sclerosant solution and interruption of the contrast flow injected into the portal system., Conclusion: Intrahepatic parenchymal ethanol injection is well tolerated and causes sclerosis restricted to a specific segment; however, intraportal ethanol injection causes massive hepatic necrosis and can lead to death.

Objective: To determine the nephrotoxic effects of arsenic kushta (Kushta Sam-ul-Far) in Wistar rats., Study Design: Experimental study., Place and Duration of Study: Department of Morbid Anatomy and Histopathology, University of Health Sciences, Lahore from May to August 2014., Methodology: This experimental study was conducted on 48 healthy Wistar rats, each weighing 200 - 250 grams. The rats were randomly divided into 4 experimental groups each containing 12 rats. Group I was taken as control given flour pellets. Group II was given single dose (180 mg/kg) of arsenic kushta for 2 weeks. Group III received 150 mg/kg of arsenic kushta for 12 weeks; whereas, group IV was also given 150 mg/kg of arsenic kushta for 12 weeks along with 75 mg of BSA (bovine serum albumin). Histopathological changes in glomeruli, tubules and interstitium were noted in the kidney., Results: Mesangial proliferation, thickening of basement membrane, necrosis, and interstitial edema were mainly observed in all the above groups except group I which served as control. These changes were seen in greater severity in high dose groups and the group given BSA injection along with kushta (group III, IV)., Conclusion: Herbo-mineral preparations of arsenic kushta are nephrotoxic in rats and may have similar toxic effects in human beings.

Docetaxel and paclitaxel are widely used in the treatment of various malignant neoplasms. Taxane-induced sclerosis is dose-dependent and usually not generalized. Little information on the pathogenesis of scleroderma is currently available. Here, we report a case of generalized scleroderma and a case of early-stage oedematous sclerosis, both of which presented with intense versican deposits after administration of taxane for angiosarcoma., (© 2015 British Association of Dermatologists.)

Rodent strains used in epilepsy research have various neurological characteristics. These differences were suggested to be attributed to the diverse densities of the ionotropic glutamate receptor (iGluR) subunits. However, previous studies failed to find interstrain differences in the hippocampal receptor levels. We supposed that a detailed layer-to-layer analysis of the iGluR subunits in the hippocampus might reveal strain-dependent differences in their base lines and reactions induced by pilocarpine (PILO) between two mouse strains without documented ancestors. Levels of iGluR subunits in Balb/c and NMRI mice were compared using semiquantitative immunohistochemistry. The alterations in the neuronal circuitry were validated by neuropeptide Y (NPY) and neuronal nuclear antigen (NeuN) immunostainings. Immunohistochemistry showed interstrain laminar differences in some subunits of both the control and PILO-treated animals. The seizure-induced irreversible neuronal changes were accompanied by reduced GluA1 and GluA2 levels. Their changes were inversely correlated in the individual NMRI mice by Pearson's method. Increase in NPY immunoreactivity showed positive correlation with GluA1, and negative correlation with GluA2. The NMRI strain was susceptible to PILO-induced hippocampal sclerosis, while the Balb/c animals showed resistance. Basal levels of iGluRs differ in mouse strains, which may account for the interstrain differences in their reactions to the convulsant., (Copyright © 2015 Elsevier B.V. All rights reserved.)

California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Mesenteric phlebosclerosis (MP) is a relatively rare disease of the colon. An association between MP and Chinese herbal medicine intake has recently been recognized., Subjects and Methods: In the present study, we investigated the association between MP and Chinese herbal medicine intake in 42 patients, including those reported in the literature as well as those treated by us., Results: Approximately 90% patients treated by us reported a history of Chinese herbal medicine intake, particularly kamishoyosan, orengedokuto, and sanshishi (gardeniae fructus), the lattermost being consumed by the majority of patients as a crude herbal medicine., Discussion: Several MP patients report a history of Chinese herbal medicine intake. Furthermore, symptoms are exacerbated in MP patients who continue to consume the medicine after onset. Interestingly, MP was reported to develop in a married couple who had consumed the same Chinese herbal medicine for a prolonged period. These findings suggest that the intake of Chinese herbal medicine, particularly sanshishi, is strongly associated with MP development.

Objective: The objective of our study was to assess the frequency, location, extent, and patterns of bone sclerosis occurring in patients with multiple myeloma (MM) during bortezomib-based therapy., Materials and Methods: From June 2003 through December 2011, 593 whole-body reduced-dose MDCT studies were performed of 79 consecutive patients receiving bortezomib. The median surveillance time was 21 months (range, 3-67 months). Baseline studies were compared with follow-up studies during therapy (follow-up 1), at the end of therapy (follow-up 2), and 12 months after cessation of bortezomib therapy (follow-up 3). We recorded any sclerotic change occurring inside or along the margins of the osteolytic lesions, in the cancellous bone, or inside preexistent medullary or extramedullary lesions. The time point of occurrence of bone sclerosis was correlated with the best hematologic response category., Results: Fourteen (17.7%) patients developed focal (n = 11) or diffuse (n = 3) bone sclerosis. The time window from bortezomib initiation to radiographic detection of bone sclerosis was 8 months (SD, 7 months). Sclerosis occurred at multiple sites (n = 7) or at an isolated site (n = 7). On subsequent whole-body reduced-dose MDCT studies, sclerosis further increased in seven (50%) patients. Hematologic best response during bortezomib treatment was complete response (n = 1), very good partial response (n = 2), partial response (n = 8), and stable disease (n = 3). Radiologic response at the time of sclerosis detection was partial response (n = 8), stable disease (n = 2), and progressive disease (n = 4)., Conclusion: Bone remineralization may occur during bortezomib-based therapy for MM in a substantial proportion of patients. The extent, location, and patterns of sclerosis differ among patients and are unpredictable. Sclerosis was documented even in patients showing suboptimal hematologic response.

There was performed a study of carcinogenicity of benzidinsulfon (4.4'-diaminodiphenil sulfone) in rats and mice. Experimental animals (99 mice and 99 rats, approximately equally divided by sex) received the drug throughout the life by subcutaneous injections (once a week) or addition to food (5 times a week). A single dose per animal in rats was: subcutaneous administration--50 mg (in females it was reduced due to the toxicity after beginning of the experiment to 25 mg) in 0.5 ml of oil, while feeding--20 mg in 0 5 ml of oil; in mice--respectively 5 mg in 0.2 ml of oil, and 2 mg in 0, 2 ml of oil. The maximum amount of a substance when administered subcutaneously to male rats was 5.65 g, to female rats--2, 68 g, when fed to rats 12.44 g, when injected subcutaneously in mice--380 mg, when fed--737 mg. The survival of experimental animals was significantly reduced as compared to the intact control because of the toxic effect of the drug, preferably chronic nephrosis with nephritic component and secondary nephrosclerosis and as well as miocardiosclerosis and aortic sclerosis. Frequency and timing of detection of tumors in experimental animals was not significantly different from that observed in the control that indicated the absence of carcinogenic features of benzidinsulfon.

Thiopurines play a pivotal role in the management of inflammatory bowel disease. Azathioprine and mercaptopurine have been associated with a number of liver abnormalities, including hepatitis, veno-occlusive disease, nodular regenerative hyperplasia, and peliosis hepatitis. Patients treated with azathioprine and mercaptopurine have their liver chemistry tests routinely checked due to this potential for hepatotoxicity. Hepatoportal sclerosis is a cause of non-cirrhotic portal hypertension that is increasingly being recognized; its etiopathogenesis is not well defined. We present the first case report of mercaptopurine-induced hepatoportal sclerosis leading to non-cirrhotic portal hypertension in a patient with Crohn's disease. He had been treated with mercaptopurine for five years, and his liver chemistry tests were always within normal limits. This case underscores the potential serious liver adverse events that may arise silently and go undetected during treatment with mercaptopurine, and should alert clinicians as to the potential need to discontinue mercaptopurine in this setting., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted.

Objectives: To evaluate the sclerotic effect of bleomycin on the submandibular gland histopathologically and assess it as a possible alternative therapy for sialorrhea., Methods: An experimental model was designed and 18 New Zealand white rabbits were used. The rabbits were divided into two groups: a bleomycin group (n=9) and a sham group (n=9). The submandibular glands of the bleomycin group were injected with 0.3 ml bleomycin (3mg/ml) while the sham group received 0.3 ml saline. Four weeks after the procedure, the glands were removed. Histopathological studies including hematoxylin-eosin and Masson's trichrome stain were carried out. The glands were evaluated for tissue inflammation, fibrosis, edema, lipomatosis, atrophy and congestion. To investigate apoptosis, terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-11-dUTP nick-end labeling (TUNEL) immunohistochemical staining was used., Results: In the group injected with bleomycin, inflammation (n=8), edema (n=4), fibrosis (n=3), congestion (n=4) and lipomatosis (n=7) were observed. In the sham group, only lipomatosis was observed. The TUNEL assay results were 5.06 ± 1.18 (p<0.05) for acinar cells and 8.46 ± 0.82 (p<0.05) for ductal cells in the bleomycin group. This was significantly different from the results in the sham group., Conclusions: Apoptosis, inflammation, fibrosis, edema, lipomatosis and congestion were observed in the ductal and acinar cells of the bleomycin group. Bleomycin may be an alternative treatment for sialorrhea cases. However, more research is needed., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The reaction of various tissues of rats to implantation of polyhydroxyalkanoate films and ultrafine fibers was studied by optic microscopy. Implantation of polyhydroxyalkanoate films into the abdominal cavity caused a peritoneal reaction, leading after 1 month to the formation of fibrous adhesions between polyhydroxyalkanoate and intestinal loops. Under the skin and in the muscle tissue polyhydroxyalkanoate films were encapsulated in a thick fibrous capsule. Implantation of polyhydroxyalkanoate ultrathin fibers led to formation of foreign body granulomas in all tissues with perifocal inflammation and sclerosis of the adjacent tissues. The polymer was fragmented in these granulomas and phagocytosed by macrophages with the formation of giant foreign body cells. Hence, polyhydroxyalkanoate materials implanted in vivo caused chronic granulomatous inflammatory reaction and were very slowly destroyed by macrophages.

A 59-year-old woman had been admitted to our hospital every two months for over a past year because of severe right abdominal pain. Colonoscopy revealed dark blue mucosa extending from the cecum to the transverse colon, and abdominal computed tomography showed wall thickening and linear calcification along the wall from the cecum to the transverse colon. Based on these findings, the patient was given a diagnosis of idiopathic mesenteric phlebosclerosis. Subsequently, we found that she had been a long-term user of a Chinese herbal product containing Gardeniae fructus for allergic rhinitis. After discontinuing the product, the patient has been free of abdominal pain for a year.

Background: Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, characterised by thickening of the wall of the right hemicolon with calcification of mesenteric veins. However, the aetiology remains unknown., Aim: To investigate the possible association of herbal medicines with IMP., Method: The clinical data of four of our own patients were collected. Furthermore, we searched for previous reports about similar patients with detailed descriptions of herbal prescriptions that they had taken. We compared herbal ingredients to identify the toxic agent as a possible aetiological factor., Results: Clinical data on a total of 25 patients were summarised. Mean age was 61.8 years and there was female predominance (6 men and 19 women). The used Kampo prescription, the number of cases, and the mean duration of use were as follows: kamisyoyosan in 12 cases for 12.8 years, inshin-iseihaito in 5 cases for 13.4 years, orengedokuto in 4 cases for 14.3 years, inchinkoto in 1 case for 20 years, kamikihitou in 1 case for 19 years, seijobofuto in 1 case for 10 years and gorinsan in 1 case for an unknown duration. Only one ingredient, sansisi, was common to the herbal medicines of all 25 patients. This crude drug called geniposide in English is a major constituent of the Gardenia fruits., Conclusion: The long-term use of geniposide in herbal medicines appears to be associated with mesenteric phlebosclerosis., (© 2012 Blackwell Publishing Ltd.)

Varicocele is treated by different surgical techniques, none of which is yet acknowledged as the "gold standard." Some of these techniques, especially microsurgical techniques, are very time consuming and thus expensive, and the treatment of varicocele still causes some complications and recurrences. Marmar and Kim's technique presents some indisputable advantages: it allows the preservation of the arteries and seems to offer the highest percentage of success and lowest number of complications. The authors modified and simplified the microsurgical technique of Marmar and Kim, using a subinguinal approach with intraoperative antegrade sclerotherapy of dilated veins. After the cord has been clamped, 1.5 to 3 mL of 3% aetoxisclerol mixed with 0.5 mL of air is injected. Commonly, minor complications can occur. The most common complication is transient penile lymphangitis, the cause of which is unclear. As the procedure allows selective sparing of the lymphatic vessels, it avoids hydrocele due to the performed procedure.

Activation of fibroblasts by interleukin-6 (IL-6) is implicated in the pathogenesis of scleroderma, suggesting that the inhibition of fibroblast activation may be a promising scleroderma treatment. In this study, we used an IL-6 blocking antibody (Ab) and Il-6 knockout (Il-6KO) mice to examine the role of IL-6 in the bleomycin (BLM)-induced mouse model of scleroderma. BLM was administered to C57BL/6 and Il-6KO mice to induce dermal sclerosis. BLM-treated and control phosphate-buffered saline-treated mice were treated with anti-mouse IL-6 receptor monoclonal Ab (MR16-1). Disease severity was evaluated by measuring dermal thickness and skin hardness, by counting the numbers of α-smooth muscle actin-positive cells and mast cells, and by examining the cutaneous draining lymph nodes. C57BL/6 mice with BLM induced scleroderma had elevated serum IL-6 levels and more severe dermal sclerosis than Il-6KO mice. Weekly administration of MR16-1, but not control Ab, prevented and improved dermal sclerosis, and also attenuated swelling of the draining lymph nodes. MR16-1 suppressed α-smooth muscle actin induction in IL-6-stimulated Il-6KO fibroblasts. Our results indicate that IL-6 contributes to BLM induced dermal sclerosis and that IL-6 receptor-specific monoclonal Ab may improve the symptoms of scleroderma by suppressing fibroblast activation., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

In this study, we performed immunohistochemistry for somatostatin (SS), neuropeptide Y (NPY), and parvalbumin (PV) in LiCl-pilocarpine-treated rats to observe quantitative changes and axonal sprouting of GABAergic interneurons in the hippocampus, especially in the sclerotic hippocampus. Fluoro-Jade B (FJB) was performed to detect the specific degeneration of GABAergic interneurons. Compared with age-matched control rats, there were fewer SS/NPY/PV-immunoreactive (IR) interneurons in the hilus of the sclerotic hippocampus in pilocarpine-treated rats; hilar dentritic inhibitory interneurons were most vulnerable. FJB stain revealed degeneration was evident at 2 months after status epilepticus. Some SS-IR and NPY-IR interneurons were also stained for FJB, but there was no evidence of degeneration of PV-IR interneurons. Axonal sprouting of GABAergic interneurons was present in the hippocampus of epileptic rats, and a dramatic increase of SS-IR fibers was observed throughout all layers of CA1 region in the sclerotic hippocampus. These results confirm selective loss and degeneration of a specific subset of GABAergic interneurons in specific subfields of the hippocampus. Axonal sprouting of inhibitory GABAergic interneurons, especially numerous increase of SS-IR neutrophils within CA1 region of the sclerotic hippocampus, may constitute the aberrant inhibitory circum and play a significant role in the generation and compensation of temporal lobe epilepsy.

The purpose of this study was to report significant alterations in orbital vasculature following combined systemic chemoreduction/laser ablation and periocular carboplatin treatment and to discuss treatment implications in two cases of advanced retinoblastoma. Assessment of orbital and ophthalmic vasculature was done following nine cycles of systemic chemotherapy. Intra-arterial chemotherapy was provided 6 months following completion of systemic chemoreduction, when the tumor was clearly active and progressive. Orbital angiography of both eyes, performed prior to the intra-arterial melphalan injection, documented sclerosis of the ophthalmic artery vasculature with delayed transit time, decreased choroidal blush, and anomalous vessels in the eye receiving periocular carboplatin injections. The orbital vasculature in the contralateral eye was not affected. Orbital and ophthalmic vascular alterations may occur with the use of combined systemic chemotherapy and periocular carboplatin. Systemic chemotherapy and focal transpupillary laser tumor ablation, alone, did not appear to impact the orbital and ophthalmic vascular supply. Impaired vascular supply may have significant influence on the impact of the efficacy of standard and future experimental therapeutic options., (Copyright 2010, SLACK Incorporated.)

Glutamine is the most important donor of NH(3) in kidney playing an important role in acid-base buffering system. Besides this effect, glutamine presents many other relevant functions in the whole body, such as a precursor of arginine in adult and neonates. In addition to these effects, some studies have shown that glutamine can potentiate renal disease. In the present study, the effect of short-term treatment (15 days) with glutamine on control and diabetic rats was investigated. Using biochemical, histological and molecular biology analysis from control and diabetic rats we verified that glutamine supplementation increase in pro-inflammatory interleukins (IL)-1beta and IL-6 content in renal cortex and induce alteration in glomerular characteristics. This study showed that short-term treatment with glutamine in association with increased glucose levels could cause important alterations in glomerular morphology that may result in fast progression of kidney failure.

Objectives: The objective of the present study was to determine the effect of zinc aspartate on myringosclerosis in perforated rat tympanic membrane., Patients and Methods: Fifteen Sprague-Dawley rats were randomly divided into three groups each containing five rats. Automicroscopic examinations were performed and then all rats were bilaterally myringotomized. Group 1 received no treatment. Group 2 was treated with intraperitoneal injection of physiological saline and group 3 with intraperitoneal injection of zinc aspartate. Tympanic bullas were harvested after 20 days. Histopathological evaluation was carried out under the light microscope., Results: When the groups were compared in the light of the myringosclerotic findings, while there was no significant difference between group 1 and 2 (p=1.00), it was found that there were significant differences between group 1 and 3, and between group 2 and 3 (p<0.03)., Conclusion: It appears that zinc aspartat treatment has beneficial effects on prevention or retardation of the development of myringosclerosis, but further studies are needed to clarify this effect.

We report a rare case in which triamcinolone acetonide particles gathered on posterior lens capsule after injection of intravitreal triamcinolone acetonide. Intravitreal injection of triamcinolone acetonide is useful in the treatment of macular edema; however, accumulation of triamcinolone acetonide particles on the posterior lens capsule may decrease visual acuity and requires surgical treatment.

This case report describes a patient with elbow contracture due to phlebosclerosis induced by anti-cancer drug infusion. Limitation of elbow extension was completely relieved by surgical excision of the sclerotic vein.

Objective: By examination of the original Yellow Card data to determine the duration of the latent period of the sclerosing peritonitis which formed part of the oculomucocutaneous syndrome that was associated with practolol, the beta-adrenergic receptor blocking agent that was withdrawn from clinical usage in the UK in December 1975 in response to reports of the syndrome., Method: Relevant drug analysis prints (DAPs) for practolol were obtained from the Medicines and Healthcare Products Regulatory Agency (MHRA) and, by application to the Interim Committee on Yellow Card data, copies were obtained of the anonymised Yellow Card reports for all the 201 cases of sclerosing peritonitis that were reported in patients treated with practolol. These data were used to determine the latent period of this iatrogenic adverse drug reaction., Results: It was shown that no other cause than practolol operated in all or a majority of the cases of sclerosing peritonitis and the suspected adverse reaction could properly be attributed to the drug. The latent period (the time period between the drug start date and the reaction start date) of the sclerosing peritonitis associated with practolol averaged 201 weeks (range 26-606 weeks; standard deviation 130 weeks)., Conclusion: The latent period of the sclerosing peritonitis that formed part of the practolol oculomucocutaneous syndrome averaged about 4 years and had a range of from 0.5 to over 11.5 years. The Yellow Card Scheme could detect this ultra long-latency adverse reaction.

Objectives: Myringosclerosis is a common sequela of ventilation tube insertion for the treatment of the otitis media with effusion. Several antioxidants have been identified to prevent myringosclerosis. The objective of this study was to investigate the effect of caffeic acid phenethyl ester (CAPE) on the prevention of experimentally induced myringosclerosis., Methods: Thirty-five Sprague-Dawley rats were unilaterally myringotomized. The rats were divided into four groups randomly: group 1 received no treatment, group 2 received intraperitoneally administered saline and group 3 received intraperitoneally administered CAPE. The tympanic membranes were examined by otomicroscopy on the 15th day after treatment. The membranes were then harvested and evaluated histologically by light microscopy., Results: The tympanic membranes from group 1 showed extensive myringosclerosis; those from group 2 showed a similar occurrence of myringosclerosis. However, group 3 had a reduced occurrence of myringosclerosis by otomicroscopic evaluation. Under light microscopic examination, the lamina propria of the pars tensa was found to be thicker and more sclerotic in groups 1 and 2 when compared with group 3., Conclusions: Systemic treatment with CAPE was found to be effective in the prevention of sclerotic lesions in myringotomized rat tympanic membranes.

Simple liver cysts are congenital with a prevalence of 2.5%-4.25%. Imaging, whether by US, CT or MRI, is accurate in distinguishing simple cysts from other etiologies, including parasitic, neoplastic, duct-related, and traumatic cysts. Symptomatic simple liver cysts are rare, and the true frequency of symptoms is not known. Symptomatic simple liver cysts are predominantly large (> 4 cm), right-sided, and more common in women and older patients. The vast majority of simple hepatic cysts require no treatment or follow-up, though large cysts (> 4 cm) may be followed initially with serial imaging to ensure stability. Attribution of symptoms to a large simple cyst should be undertaken with caution, after alternative diagnoses have been excluded. Aspiration may be performed to test whether symptoms are due to the cyst; however, cyst recurrence should be expected. Limited experience with both laparoscopic deroofing and aspiration, followed by instillation of a sclerosing agent has demonstrated promising results for the treatment of symptomatic cysts. Here, we describe a patient with a large, symptomatic, simple liver cyst who experienced complete resolution of symptoms following cyst drainage and alcohol ablation, and we present a comprehensive review of the literature.

Among the bisphosphonates, the nitrogen-containing bisphosphonates have much stronger anti-bone-resorptive activities than bisphosphonates containing no nitrogen, but nitrogen-containing bisphosphonates mostly have inflammatory side effects. Our previous murine-model experiments with a single intraperitoneal bisphosphonate injection demonstrated that (i) nitrogen-containing bisphosphonates induce various inflammatory reactions via an IL-1-dependent mechanism, (ii) alendronate (an nitrogen-containing bisphosphonate) produces a clear sclerotic line in the tibia that is easily detectable by radiography a few weeks later (tentatively called the bisphosphonate line, a useful marker for the anti-bone-resorptive activities of bisphosphonates), and (iii) clodronate (a non-nitrogen-containing bisphosphonate) reduces the inflammatory reactions induced by alendronate but does not reduce the bisphosphonate line formation induced by alendronate. We compared the effects of clodronate, aspirin and dexamethasone on the inflammatory reactions induced by alendronate (40 micromol/kg) (induction of the histamine-forming enzyme, accumulation of pleural exudate and splenomegaly) and on the bisphosphonate line formation induced by alendronate (0.1 micromol/kg). The effects of aspirin (833 micromol/kg) were weak. However, like clodronate, dexamethasone (10 micromol/kg, injected 5 min. after alendronate), strongly inhibited the alendronate-induced inflammatory reactions but did not reduce the alendronate-induced bisphosphonate line formation. Alendronate produced normal bisphosphonate lines in IL-1-deficient mice, too. These results suggest that clodronate and/or dexamethasone may be suitable for preventing or reducing the inflammatory side effects of nitrogen-containing bisphosphonates while preserving their powerful anti-bone-resorptive activities (although in practice the known side effects of dexamethasone may limit its use), and that the anti-bone resorptive activities of nitrogen-containing bisphosphonates are not influenced by IL-1.

We explored the acute and long-term effects of short-lived, intense oxidative stress on peritoneal permeability and structure, induced with intraperitoneal injection of the oxidant agent deoxycholate, in rats. Ten minutes after the experimental intervention, peritoneal dialysis, performed over an exposure time of 60 minutes, revealed an increased urea dialysate/plasma ratio, greater glucose absorption, increased albumin losses in the effluent dialysate, and a reduced ultrafiltration rate. Mesothelial-cell imprints taken from the anterior liver surface indicated a substantially decreased density in the cell population. After the recovery period of 30 days, all alterations were still evident. Additionally, macroscopic and histologic observations made at this time interval detected peritoneal fibrosis and sclerosis, characterized by peritoneal adhesions, wrapping of intestinal loops, and the presence of a layer of fibrous tissue dressing the cavitary aspect of the liver peritoneal envelope. This report describes a reproducible experimental model of peritoneal fibrosis induced by acute oxidative injury. On the basis of these findings, it may be speculated that functional and structural alterations observed in patients are related to long-term continuous exposure of the monolayer to oxidative injury resulting from the high concentrations of d-glucose present in peritoneal dialysis solutions.

Objective: - Recent studies have suggested that valvular calcification in calcific aortic stenosis (AS) may be actively regulated. "Receptor Activator of Nuclear factor kappaB Ligand" (RANKL) and osteoprotegerin (OPG) are members of a cytokine system involved in bone turnover and vascular calcification. Their role in calcific AS is not known., Methods and Results: - By immunohistochemistry using human aortic valves, RANKL was not expressed at relevant levels in controls but detectable in AS. OPG expression was marked in controls but significantly lower in AS. Areas containing focal calcification exhibited significantly less OPG-positive cells as compared to non-calcified regions. Stimulation with RANKL lead to a significant rise in matrix calcification, nodule formation, alkaline phosphatase activity, expression of the bone-type isoenzyme of alkaline phosphatase, and expression of osteocalcin in cultured human aortic valve myofibroblasts. Moreover, RANKL increased DNA binding of the essential osteoblast transcription factor cbfa-1., Conclusion: - RANKL and OPG are differentially expressed in calcific AS. In cultured human aortic valve myofibroblasts, RANKL promotes matrix calcification and induces the expression of osteoblast-associated genes, indicating a transition towards an osteogenic phenotype. These results suggest that the RANKL-OPG pathway may regulate valvular calcification in calcific AS?

Vitamin D intoxication in infancy has serious consequences attributable to acute hypercalcemia and subsequent hypercalcuria/nephrocalcinosis. Current treatments of patients with vitamin D intoxication are unsatisfactory and associated with prolonged hypercalcemia. We now report the use of oral alendronate sodium in a 3-month-old infant with vitamin D intoxication. Short-term oral alendronate sodium treatment effectively corrected hypercalcemia/hypercalciuria, decreased the duration of hospitalization, and appears safe in 15 months of observation.