The physical manifestations of aging reflect a loss of homeostasis that effects molecular, cellular and organ system functional capacity. As a sentinel homeostatic pathway, changes in apoptosis can have pathophysiological consequences in both aging and disease. To assess baseline global apoptosis balance, sera from 204 clinically normal subjects had levels of sFas (inhibitor of apoptosis), sFasL (stimulator of apoptosis), and total cytochrome c (released from cells during apoptosis) measured. Serum levels of sFas were significantly higher while sFasL and cytochrome c levels were lower in men compared to women. With increasing age there was a decrease in apoptotic markers (cytochrome c) and pro-apoptotic factors (sFasL) and an increase in anti-apoptotic factors (sFas) in circulation. The observed gender differences are consistent with the known differences between genders in mortality and morbidity. In a separate cohort, subjects with either breast (n = 66) or prostate cancer (n = 38) exhibited significantly elevated sFas with reduced sFasL and total cytochrome c regardless of age. These markers correlated with disease severity consistent with tumor subversion of apoptosis. The shift toward less global apoptosis with increasing age in normal subjects is consistent with increased incidence of diseases whose pathophysiology involves apoptosis dysregulation.

No abstract

A 67-year-old male with a past medical history of chronic kidney insufficiency, splenectomy, and recurrent babesiosis infection was transferred to with jaundice and abdominal pain.The patient initially presented to an outside hospital (OSH) with generalized weakness, chills, and gastrointestinal symptoms and was found to have Babesia on peripheral blood smears. The patient received seven days of azithromycin and atovaquone, followed by three days of clindamycin and quinine sulfate. The patient was discharged home with improved symptoms and a negative peripheral blood smear. Less than 24 hours later he returned to the OSH with worsening myalgias and abdominal pain. Physical exam was significant for jaundice and hepatomegaly. Laboratory data revealed anemia, elevated creatinine, bilirubin of 30 mg/dL, and 1% parasitemia. At this point the patient was transferred for further management.Patient's past medical history was significant for chronic renal insufficiency, congestive heart failure, type 2 diabetes mellitus, coronary artery disease, and hypertension. Previous surgical procedures included splenectomy after a motor vehicle accident, below the knee amputation (BKA) of the right leg, and cholecystectomy. Patient denied alcohol or substance abuse, and quit smoking tobacco approximately 10 years ago. He is a retired carpenter and denied any recent history of travel. Medications on admission included digoxin, clopidogrel, isosorbide mononitrate, carvedilol, sucralfate, esomeprazole, metoclopramide, amlodipine, octreotide, and insulin lispro.On examination, patient looked fatigued, but in no acute distress. He was afebrile and had stable vital signs. Physical exam was significant for scleral icterus, ventral hernia and diffuse blanching, maculopapular rash on patient's hands and soles.Patient was admitted and started on treatment with clindamycin and quinine. The patient's blood smear showed Babesia species with a 1.7% parasitemia (figure 1). During the hospital stay, patient had an acute mental status change with asterixis. Laboratory data obtained at that time revealed elevated INR, bilirubin, and ammonia levels. Given the clinical findings, patient was started on lactulose for possible hepatic encephalopathy. Hepatitis serology was found to be negative. Dialysis was initiated in the setting of acute renal failure. Patient's clinical status continued to worsen, so red blood cell exchange transfusion was initiated in an attempt to reduce the parasite load and help clear the infection. Despite the exchange transfusion and continued antibiotic treatment, the patient continued to have hemolysis, paracitemia, renal failure, and hepatic failure. At that point hospice discussion was initiated and patient was eventually transferred to hospice home care.