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Purpose of Review: To review the clinical characteristics of paroxysmal hypertension (pseudopheochromocytoma), its previously unsuspected cause, and effective treatment approaches. Recent Findings: Patients with paroxysmal hypertension experience recurrent, sudden, unprovoked, symptomatic, and severe elevations of blood pressure that occur independently of current stress or perceived emotional distress. Recent findings point to a previously unsuspected psychosomatic etiology, linked in most to a past history of abuse, trauma, or prolonged severe stress, often with repression of pertinent emotions, or to a repressive coping style. Consistent with this understanding, treatment with an antidepressant is thus far the only pharmacologic intervention demonstrated to be effective in preventing recurrent paroxysms, and is effective in most patients. Other treatment approaches are discussed, including medications to acutely lower blood pressure during paroxysms, and, in some cases, the possibility of emotional healing. Summary: Recent findings indicate that paroxysmal hypertension is a psychosomatic disorder frequently linked to a past history of trauma or prolonged severe stress, usually with longstanding repression of pertinent emotions. Data strongly encourage treatment with an antidepressant in patients with recurrent or severe paroxysms. Further studies are needed. [ABSTRACT FROM AUTHOR]

Neuronal active Caspase-6 (Casp6) is associated with Alzheimer disease (AD), cognitive impairment, and axonal degeneration. Caspase-1 (Casp1) can activate Casp6 but the expression and functionality of Casp1-activating inflammasomes has not been well-defined in human neurons. Here, we show that primary cultures of human CNS neurons expressed functional Nod-like receptor protein 1 (NLRP1), absent in melanoma 2, and ICE protease activating factor, but not the NLRP3, inflammasome receptor components. NLRP1 neutralizing antibodies in a cell-free system, and NLRP1 siRNAs in neurons hampered stress-induced Casp1 activation. NLRP1 and Casp1 siRNAs also abolished stress-induced Casp6 activation in neurons. The functionality of the NLRP1 inflammasome in serum-deprived neurons was also demonstrated by NLRP1 siRNA-mediated inhibition of speck formation of the apoptosis-associated speck-like protein containing a caspase recruitment domain conjugated to green fluorescent protein. These results indicated a novel stress-induced intraneuronal NLRP1/Casp1/Casp6 pathway. Lipopolysaccharide induced Casp1 and Casp6 activation in wild-type mice brain cortex, but not in that of Nlrp1−/− and Casp1−/− mice. NLRP1 immunopositive neurons were increased 25- to 30-fold in AD brains compared with non-AD brains. NLRP1 immunoreactivity in these neurons co-localized with Casp6 activity. Furthermore, the NLRP1/Casp1/Casp6 pathway increased amyloid beta peptide 42 ratio in serum-deprived neurons. Therefore, CNS human neurons express functional NLRP1 inflammasomes, which activate Casp1 and subsequently Casp6, thus revealing a fundamental mechanism linking intraneuronal inflammasome activation to Casp1-generated interleukin-1-β-mediated neuroinflammation and Casp6-mediated axonal degeneration. [ABSTRACT FROM AUTHOR]

This study examined the role of cisplatin-induced p53 activation in regulation of caspases and cellular injury during cisplatin nephrotoxicity. The executioner caspase-6 and -7 but not caspase-3 were identified as transcriptional targets of p53 in cisplatin injury as revealed by chromatin immunoprecipitation, a reporter gene and electrophoretic mobility shift assays, and real-time PCR following overexpression and inhibition of p53. DNA binding by p53 involved the first introns of the human and mouse caspase-7 gene and the mouse caspase-6 gene. Studies in human kidney, breast, ovary, colon, and prostate tumor cell lines also validated these findings. Treatment of p53 (−/−) cells with cisplatin did not induce caspase-6 and -7 expression and subsequent activation. In caspase-3 (−/−) cells, inhibition of caspase-6 and -7 activations markedly prevented cisplatin-induced cell death. In an in vivo model of cisplatin nephrotoxicity inhibition of p53 activation by a p53 inhibitor suppressed transactivation of the caspase-6 and -7 genes and prevented renal failure. p53 (−/−) mice were resistant to cisplatin nephrotoxicity as assessed by renal function and histology. These studies provide first evidence for p53-dependent transcriptional control of the caspase-6 and -7 genes and its functional significance in cisplatin injury to renal cells and functional implication of cisplatin-induced p53 induction in vitro and in vivo in cisplatin nephrotoxicity.Cell Death and Differentiation (2008) 15, 530–544; doi:10.1038/sj.cdd.4402287; published online 7 December 2007 [ABSTRACT FROM AUTHOR]

Eupatorium adenophorum (Crofton weed), a native of Central America, has appeared as a major weed in several areas in different parts of the world. Horses that eat this plant are poisoned on prolonged exposure. Toxicity due to consumption of this plant by other grazing animals is not clear. Administration of freeze-dried leaf powder to mice results in hepatotoxicity. Earlier attempts to produce toxicity in rats using the leaves of this plant were not successful. In the present study, administration of oven-dried E. adenophorum leaves collected at the flowering stage elicited hepatotoxicity in rats. The affected animals had a marked increase in the concentration of plasma bilirubin and in the activities of 5′-nucleotidase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase. There were no significant differences in plasma creatinine, urea or total protein values in the affected animals compared to controls. The livers of the affected animals had focal areas of necrosis throughout the parenchyma and hepatocytes showed megalocytosis. The bile ducts were dilated and the epithelium showed degenerative to necrotic changes. The alterations in bilirubin, enzymes and histopathological changes imply cholestasis and liver injury. [ABSTRACT FROM AUTHOR]

A 10-year-experience with 42 cases of teratomas in paediatric age group is presented. The commonest type of teratoma was sacrococcygeal followed by ovarian and retroperitoneal teratomas. An analysis of clinical profile, malignant potential, management, prognostic factors and follow up is discussed with review of literature. [ABSTRACT FROM AUTHOR]

Effective treatment modalities for locally advanced squamous cell carcinoma of the head and neck are limited and seldom result in long term survival. The improved results with cisplatin chemotherapy are encouraging and represent an additional therapeutic modality for head and neck cancer. To estimate the effectiveness, safety and tolerance of simultaneous cisplatin and radiotherapy in advanced carcinoma of the head and neck this phase II study was undertaken. 40 eligible patients with advanced squamous cell carcinoma of the head and neck were entered into the study. Group I (20 patients) received conventional radical radiation 64 Gy/32 F/6.5 weeks and Group II (20 patients) received in addition to above radiotherapy, concomitant cisplantin 100 mg/m every 3 weeks for three doses with forced diuresis and antiemetic schedule, on day 1, 22 and 43rd of rediation treatment. The complete response with RT alone was 40% and with combined treatment 70%. The treatment tolerance was approximately equal in both groups and all patients completed treatment in scheduled time. [ABSTRACT FROM AUTHOR]

Pancreatoblastoma is an extremely rare pancreatic tumor in childhood, comprising 0.5% of pancreatic non endocrine tumors. Just over 50 cases have been reported in the literature till 1997. A 10 year-old male child presented with mass abdomen of 9 months duration. USG and CT abdomen showed a large mixed density lobulated mass in abdomen anterior to, and displacing down the portal vein and splenic veins. Exploratory laparotomy revealed a large mass, arising from body and tail of pancreas, not infiltrating the adjacent structures. Complete excision of the mass along with removal of body and tail of pancreas was done. The histopathological examination revealed pancreatoblastoma. He is well without any evidence of disease 6 months after the operation. To the best of our knowledge this is the first case of pancreatoblastoma with a large size (25 x 20 x 15 cm,) weight 2.5 kg, which was localized and where complete excision was possible. The largest size reported in the literature reviews has been around 15 cm. The literature review confirms that an aggressive surgical attack on resectable pancreatoblastoma may often be curative. The role of adjuvant chemotherapy or radiotherapy is still under discussion due to small number of patients treated as yet. [ABSTRACT FROM AUTHOR]

Discusses a study which examined the role and regulation of activation of caspases in cisplatin-induced injury to renal tubular epithelial cells. Methodology; Results; Conclusion.

Background: Evaluation of the ortho-anesthetic geriatric care pathway for patients with proximal femur fracture in a tertiary care referral center was done by reporting the peri-operative morbidity and mortality. Clinical and demographic predictors of mortality were also identified in this cohort., Material and Methods: This prospective observational study was conducted between August 2017 and November 2018. Demographic, anesthetic and surgical characteristics were recorded. Telephonic post-discharge follow-up was done for a period of 2 years. Factors predicting mortality were estimated using multivariate logistic regression., Results: The cohort was characterized by frailty, high ASA physical status, NYHA class and Charlson co-morbidity index. The delay in presentation to hospital and subsequent surgical fixation was 7 (1-8) and 8 (5-13) days, respectively. The 30, 60, 90-day, 1-year and 2-year mortality was 13.6%, 21.8%, 25.45%, 36.5% and 44%, respectively. Intra-operative blood transfusion was a predictor of 30-day mortality (OR 9.2, 95% CI 1.02-83.17; p  = 0.048). Pre-operative respiratory dysfunction predicted 60-day (OR 11.245, 95% CI 1.38-91.58; p  = 0.024) and 90-day (OR 11.654, 95% CI 1.91-71.1; p  = 0.008) mortality. Post-operative morbidity was reported in 31 (28.1%) patients; incidence of pneumonia ( n  = 9), sepsis ( n  = 8), MI ( n  = 6), PTE ( n  = 5) and ARF ( n  = 3) were 8.18%, 7.27%, 5.45%, 4.54% and 2.72%, respectively., Conclusion: Existing pathway facilitated surgical fixation with median delay of 8 days which should be shortened to 48 h. High mortality in our cohort needs to be decreased by preventing admission delays and aggressively managing co-morbidities. Acceptable benchmark goals for pre-operative optimization of lung disease and decrease in intra-operative blood transfusion need to be incorporated in existing care pathway., Competing Interests: Conflicts of interestAll the authors declare no potential conflicts of interest (financial or non-financial)., (© Indian Orthopaedics Association 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)