No longer a blank cheque: a narrative scoping review of physician awareness of cost.

OBJECTIVES: Healthcare costs have been steadily rising, and attention to cost containment in healthcare systems is increasingly important. It has been previously established that physicians lack adequate awareness of cost in health care and that by increasing awareness, costs can be reduced. This scoping review examines cost awareness of medications, investigations and procedures and identifies potential interventions that may serve to improve physician awareness. STUDY DESIGN: A scoping review was performed to evaluate the literature based on established Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: A review of electronic databases was performed for studies regarding physician awareness of cost, including PubMed, Embase, Cochrane Central Register of Controlled Trials and Google Scholar. RESULTS: An initial 4350 citations were identified, and 76 articles were included for full text analysis. Combined, these studies assessed 18,901 physicians. The overwhelming majority (91%) found cost awareness in physicians was low and demonstrated significant room for cost reduction. Eighteen of the 76 studies assessed an intervention to improve physician awareness of cost and used either a price list (89%) or a teaching session (11%) as the primary intervention. CONCLUSIONS: Research demonstrates that there is still a lack of awareness among physicians of the costs of medications, investigations and procedures/consumables. Initial approaches using price display and teaching sessions have shown promise. Further research into best practices for education around cost, beginning in medical school and continuing into established medical and surgical practices, may lead to increased cost savings in health care.

The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens.

INTRODUCTION: Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies. METHODS: We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis. RESULTS: Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML. CONCLUSIONS: Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.

Clinico-pathological Correlation of Thyroid Nodule Ultrasound and Cytology Using the TIRADS and Bethesda Classifications.

BACKGROUND: Clinico-pathological correlation of thyroid nodules is not routinely performed as until recently there was no objective classification system for reporting thyroid nodules on ultrasound. We compared the Thyroid Imaging Reporting and Data System (TIRADS) of classifying thyroid nodules on ultrasound with the findings on fine-needle aspiration cytology (FNAC) reported using the Bethesda System. METHODS: A retrospective analysis of 100 consecutive cases over 1 year (Jan-Dec 2015) was performed comparing single-surgeon-performed bedside thyroid nodule ultrasound findings based on the TIRADS classification to the FNAC report based on the Bethesda Classification. TIRADS 1 (normal thyroid gland) and biopsy-proven malignancy referred by other clinicians were excluded. Benign-appearing nodules were reported as TIRADS 2 and 3. Indeterminate or suspected follicular lesions were reported as TIRADS 4, and malignant-appearing nodules were classified as TIRADS 5 during surgeon-performed bedside ultrasound. All the nodules were subjected to ultrasound-guided FNAC, and TIRADS findings were compared to Bethesda FNAC Classification. RESULTS: Of the 100 cases, 74 were considered benign or probably benign, 20 were suspicious for malignancy, and 6 were indeterminate on ultrasound. Overall concordance rate with FNAC was 83% with sensitivity and specificity of 70.6 and 90.4%, respectively. The negative predictive value was 93.8%. CONCLUSION: It is essential for clinicians performing bedside ultrasound thyroid and guided FNAC to document their sonographic impression of the nodule in an objective fashion using the TIRADS classification and correlate with the gold standard cytology to improve their learning curve and audit their results.

Negative surveillance endoscopy occurs frequently in patients with short-segment non-dysplastic Barrett's esophagus.

Surveillance endoscopy of non-dysplastic Barrett's esophagus (NDBE) that fails to detect intestinal metaplasia (IM), or negative surveillance, is known to occur in clinical practice, although the frequency and possible outcomes in a large cohort in clinical practice is not well described. The goals of this study were to define frequency in which negative surveillance occurs and endoscopic outcomes in a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of patients newly diagnosed with short segment NDBE at an outpatient academic tertiary care center between 2003 and 2011 were reviewed. Only those with one or more surveillance endoscopies were included to define a frequency of negative surveillance. Included patients were further assessed if they had two or more surveillance endoscopies and were classified into groups as sampling error or negative IM on consecutive surveillances based on the results of their surveillance endoscopies. The frequency of a negative surveillance endoscopy in all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for IM of 468 total surveillance exams). A negative surveillance endoscopy occurred in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on consecutive surveillance endoscopies in 55.88% of those with ≥ 2 surveillance endoscopies and an initially negative surveillance exam. The frequency of negative IM on consecutive surveillances was 19.00% of all patients who had two surveillance endoscopies. When the index diagnostic Barrett's esophagus segment length was < 1 cm, 32.14% (18/56) of all patients (with ≥ 2 surveillance endoscopies) had negative IM on consecutive surveillance endoscopies. Negative surveillance occurs frequently in short-segment NDBE. When an initial negative surveillance endoscopy occurs, it may be due to either a sampling error or lack of detectable IM on surveillance exam. When a <1 cm segment of NDBE is diagnosed, a significant proportion of patients may go on to have continuously undetected IM on consecutive surveillance endoscopic exams without intervention.

Effects of the Decrease in Blood Lead Levels on Renal and Neurological Functions Among Occupationally Exposed and Unexposed Populations of South India: A Cohort Study.

INTRODUCTION: Exposure to lead in excess of the permissible limit is a known risk factor leading to preventable morbidity. The present study aimed to assess whether there is a change in the neurological and renal parameters among adults with blood lead levels (BLLs) higher than recommended at baseline and after prevention among differently exposed adults. METHODOLOGY: In the Guntur District of Andhra Pradesh, India, a cohort study was carried out in 2022-2023 among 180 adult males and females aged 20 to 60 years in three groups: direct occupational exposure, indirect occupational exposure, and no occupational exposure. If the blood levels were more than or equal to 5 mcg/dL, the participant's detailed neurological examination was done at baseline and end of follow-up. During the six-month follow-up period, health education on lead awareness was given monthly. BLLs were estimated using graphite furnace atomic absorption spectrometry (GFAAS). Serum creatinine was estimated using Jaffe's modified method. On neurological examination, reflexes, power, and sensation were assessed. The vibration perception threshold was determined using a biothesiometer. A p-value less than 0.05 was considered to be statistically significant. RESULTS: Among the 180 participants, the mean BLLs at baseline were 7.15±3.06 mcg/dL. The findings revealed a statistically significant decrease in mean BLLs at baseline to end of six-month follow-up. Despite this improvement, participants with BLLs ≥5 mcg/dL still accounted for a considerable proportion, albeit reduced, particularly in Groups 1 and 2. There were no statistically significant changes observed in the proportions of participants with abnormal serum creatinine, anemia, or abnormal neurological parameters. CONCLUSION: These results suggest that while prevention activities may effectively reduce overall BLLs, there might be challenges in completely mitigating the impact on certain health parameters, such as renal and neurological functions.

Correction: A Case Report of Takotsubo Cardiomyopathy With Myxedema Coma.

[This corrects the article DOI: 10.7759/cureus.32652.].

A study to evaluate the impact of examination stress on recurrent aphthous ulceration in professional college students in Jaipur district.

AIM: Recurrent aphthous ulcers (RAU) are one of the most common and poorly understood mucosal disorders. Most of the literature suggests that stress has a causal role in RAU and it is estimated that at least 1 in 5 individuals is afflicted with RAU. Review of literature reveals that nutritional and stress factors may be of paramount importance in the occurrence and severity of RAU. To test this hypothesis we have derived a study to explore definitive relationship between nutrition, stress and RAU in professional undergraduate students. METHODS: A total of 80 undergraduate students were selected randomly for the study from professional colleges. On evaluation 50 subjects were identified to be RAU positive and the rest 30 never had ulcers. All the subjects were evaluated during their university examinations and the 50 RAU positive subjects were later evaluated for the stress levels after the examinations. The major variables that were compared were simplified oral hygiene index, body mass index, hemoglobin percentage, mid upper arm circumference and malnutrition universal screening tool, Hamilton anxiety rating scale and general health questionnaire. RESULTS: The stress level was measured using Hamilton anxiety scale (HAS) and a highly significant difference was determined between during exams and post exam period in the students who tested positive for RAU. The General Health Questionnaire (GHQ) also appeared to be a sensitive instrument to determine the stress levels and statistically significant differences were recorded in the RAU positive students during exams and post exam period. General health is also poor during exams as compared after exams. The hematological factor as denoted by HB measurement showed significant statistical difference between patients who had RAU (present and history) and those who did not. Nutritional indicator (Malnutrition Universal Screening Tool) MUST also showed that it was a sensitive measure for detecting nutritional compromise and the statistically significant difference was shown between RAU positive and negative. The BMI, OHI-S and MUAC had no statistical differences shown in our analysis. CONCLUSION: A number of conditions and diseases have been shown to lead to the onset of RAU. However, RAU can occur in the absence of any diagnosable disease or physical condition. According to our evaluation, stress emerged as having a causal role on RAU, along with hematinic deficiencies and poor nutritional status in professional undergraduate college students.

Graphene-tethered 5-fluorouracil-loaded ZnO nanocomposites for pH-responsive enhanced efficacy in drug delivery on MCF-7 cells.

Graphene-tethered ZnO nanocomposites with rod shapes and oval-shaped 5-fluorouracil-loaded graphene-supported ZnO nanohybrids were synthesized using one pot wet chemical bottom up coprecipitation method. The presence of hexagonal nanophase of ZnO lattice with surface-tethered graphene sheets were confirmed using XRD pattern and supportive UV-Vis and FTIR spectrum. XRD data of these nanocomposites were matched with TEM images which proved the hexagonal ZnO core maintained even after surface tailoring with graphene and drug loading. These porous nanocomposites were loaded with anticancer drug 5-fluorouracil for enhancement in anticancer activity on breast cancer MCF-7 cells. The optical, morphological and phase physicochemical characterizations of the nanohybrids were performed using techniques as UV-Vis, FTIR, XRD spectrometry, and TEM microscopic analysis. The nanocomposites did not only exhibit biocompatibility but also pH responsive in vitro delivery applied for anticancer therapy on the basis of spectrometric MTT assay following sustained drug release with zero-order Peppas release kinetics. These nanocomposites exhibited higher anticancer activity on MCF-7 cells than free drug after in vitro MTT assay. On the basis of these demonstrations, these newer nanocomposites find future biomedical applications in pH-responsive drug delivery.

The neglected role of relative humidity in the interannual variability of urban malaria in Indian cities.

The rapid pace of urbanization makes it imperative that we better understand the influence of climate forcing on urban malaria transmission. Despite extensive study of temperature effects in vector-borne infections in general, consideration of relative humidity remains limited. With process-based dynamical models informed by almost two decades of monthly surveillance data, we address the role of relative humidity in the interannual variability of epidemic malaria in two semi-arid cities of India. We show a strong and significant effect of humidity during the pre-transmission season on malaria burden in coastal Surat and more arid inland Ahmedabad. Simulations of the climate-driven transmission model with the MLE (Maximum Likelihood Estimates) of the parameters retrospectively capture the observed variability of disease incidence, and also prospectively predict that of 'out-of-fit' cases in more recent years, with high accuracy. Our findings indicate that relative humidity is a critical factor in the spread of urban malaria and potentially other vector-borne epidemics, and that climate change and lack of hydrological planning in cities might jeopardize malaria elimination efforts.

A Case Report of Takotsubo Cardiomyopathy With Myxedema Coma.

The exact pathogenesis of Takotsubo cardiomyopathy (TC) or broken heart syndrome is unclear. However, it is known to be a stress-induced cardiomyopathy. There are multiple causes of TC, and thyroid dysfunction is supposed to be one of the causes. We present a case of a 74-year-old female with a medical history of hypothyroidism who was admitted to the hospital with a myxedema coma and myocardial infarction. Her angiography had no evidence of plaque, thrombus, or spasm, and echocardiography showed apical ballooning, thus confirming the diagnosis of TC.

Favorably skewed X-inactivation accounts for neurological sparing in female carriers of Menkes disease.

Classical Menkes disease is an X-linked recessive neurodegenerative disorder caused by mutations in ATP7A, which is located at Xq13.1-q21. ATP7A encodes a copper-transporting P-type ATPase and plays a critical role in development of the central nervous system. With rare exceptions involving sex chromosome aneuploidy or X-autosome translocations, female carriers of ATP7A mutations are asymptomatic except for subtle hair and skin abnormalities, although the mechanism for this neurological sparing has not been reported. We studied a three-generation family in which a severe ATP7A mutation, a 5.5-kb genomic deletion spanning exons 13 and 14, segregated. The deletion junction fragment was amplified from the proband by long-range polymerase chain reaction and sequenced to characterize the breakpoints. We screened at-risk females in the family for this junction fragment and analyzed their X-inactivation patterns using the human androgen-receptor (HUMARA) gene methylation assay. We detected the junction fragment in the proband, two obligate heterozygotes, and four of six at-risk females. Skewed inactivation of the X chromosome harboring the deletion was noted in all female carriers of the deletion (n = 6), whereas random X-inactivation was observed in all non-carriers (n = 2). Our results formally document one mechanism for neurological sparing in female carriers of ATP7A mutations. Based on review of X-inactivation patterns in female carriers of other X-linked recessive diseases, our findings imply that substantial expression of a mutant ATP7A at the expense of the normal allele could be associated with neurologic symptoms in female carriers of Menkes disease and its allelic variants, occipital horn syndrome, and ATP7A-related distal motor neuropathy.

Kikuchi-Fujimoto syndrome presenting to a sexual health clinic.

We report on a 37-year-old woman who presented with a six-week history of bilateral, tender lymph nodes in her groin. An initial biopsy was done with the histology 'suggestive of lymphogranuloma venereum (LGV)'. She had not had sexual intercourse for over two years and had no symptoms or signs of note to report. Examination revealed large, smooth tender lymph nodes above the inguinal ligament bilaterally with no other areas of lymphadenopathy. Due to a possible diagnosis of LGV, three weeks of doxycycline was given. A further review of the histology slides revealed 'subacute necrotizing lymphadenitis' highly suggestive of Kikuchi-Fujimoto syndrome of unknown cause, which is usually self-limiting. Subsequent follow-up of the patient revealed a reduction in the lymph nodes size with little tenderness.

Summer Temperature and Spatial Variability of all-Cause Mortality in Surat City, India.

BACKGROUND: Ample information is available on extreme heat associated mortality for few Indian cities, but scant literature is available on effect of temperature on spatial variability of all-cause mortality for coastal cities. OBJECTIVE: To assess the effect of daily maximum temperature, relative humidity and heat index on spatial variability of all-cause mortality for summer months (March to May) from 2014 to 2015 for the urban population of Surat (coastal) city. MATERIALS AND METHODS: Retrospective analysis of the all-cause mortality data with temperature and humidity was performed on a total of 9,237 deaths for 184 summer days (2014-2015). Climatic and all-cause mortality data were obtained through Tutiempo website and Surat Municipal Corporation respectively. Bivariate analysis performed through SPSS. OBSERVATIONS: Mean daily mortality was estimated at 50.2 ± 8.5 for the study period with a rise of 20% all-cause mortality at temperature ≥ 40°C and rise of 10% deaths per day during extreme danger level (HI: > 54°C) days. Spatial (Zone wise) analysis revealed rise of 61% all-cause mortality for Southeast and 30% for East zones at temperature ≥ 40°C. CONCLUSIONS: All-cause mortality increased on high summer temperature days. Presence of spatial variation in all-cause mortality provided the evidence for high risk zones. Findings may be helpful in designing the interventions at micro level.

Physicochemical characterization of a minor mucin component from cystic fibrosis tracheobronchial secretions.

A minor mucin glycoprotein component (HTM-2) was purified from the tracheobronchial secretions of two cystic fibrosis patients using a protocol established in our laboratory. The secretions were solubilized in 0.1 M Tris-HCl buffer (pH 7.5) containing 0.22 M potassium thiocyanate and fractionated on a Bio-Gel A-5m column, followed by digestion with DNAase, rechromatography on the same column and chromatography on hydroxyapatite which resolved the major mucin (HTM-1) from the minor mucin component (HTM-2). The mucin component HTM-2 was further purified using Superose 6 chromatography. SDS-composite gel (2% polyacrylamide + 0.5% agarose) and 6% polyacrylamide gel electrophoresis showed that the purified HTM-2 was totally free of low-molecular-weight contaminants. Equilibrium density sedimentation centrifugation of purified HTM-2 using CsCl gradients also showed the absence of proteoglycans and other low-molecular-weight proteins. Comparison of carbohydrate and amino acid compositions of the two mucin components indicated that HTM-2 was quite different from the major mucin, HTM-1, reported earlier from our laboratory (Biochemistry, 24, 7334, 1985). This suggested that HTM-2 has a different polypeptide core and is perhaps a different gene product. The effects of 6 M guanidine-HCl and different concentrations of NaCl on the molecular size of HTM-2 and its ability to form aggregates was also investigated using the technique of static light scattering. In buffer containing 6 M guanidine-HCl, HTM-2 had a weight-average molecular weight of approximately 4.5 x 10(6). However, in the presence of buffer containing 0.03, 0.10 or 0.15 M NaCl, the molecular weight of HTM-2 was estimated to be approximately 11 x 10(6). These data suggest aggregation of HTM-2 in the presence of a range of NaCl concentrations. In contrast to HTM-1, which is a more anionic glycoprotein, the apparent molecular size of HTM-2 did not decrease at the higher NaCl concentration.

Pretest variables that improve the predictive value of exercise testing in women.

AIM: Graded exercise testing (GXT) is used in coronary artery disease (CAD) prevention and rehabilitation programs. In women, this test has a decreased accuracy and predictive value but there are few studies that examine the predictors of a verified positive test. The aim of this study was to determine those pretest variables that might enhance the predictive value of the GXT in women clients. METHODS: Medical records of 1761 patients referred for GXT's over a 5 yr period of time were screened. Demographic, medical, and exercise test variables were analyzed. The GXT's of 403 women were available for inclusion and they were stratified into 3 groups: positive responders that were subsequently shown to have CAD (N.=28 verified positive [VP]), positive responders that were not shown to have CAD (N.=84 non-verified positive [NVP]) and negative GXT responders (N.=291). Both univariate and a multivariate step-wise regression statistics were performed on this data. RESULTS: Pretest variables that differentiated between VP and NVP groups are: (an older age=65.8 vs. 60.2 yrs. P<0.05; a greater BMI=30.8 vs. 28.8 kg/m2; diabetes status or an elevated fasting glucose =107.4 vs. 95.2 mg/dL P<0.05; and the use of some cardiovascular medications. Our subsequent linear regression analysis emphasized that HDL cholesterol and beta blocker usage were the most predictive of a positive exercise test in this cohort. CONCLUSION: The American Heart Association recommends GXT's in women with an intermediate pretest probability of CAD. But there are only two clinical variables available prior to testing to make this probability decision: age and quality of chest pain. This study outlined that other pre-exercise test variables such as: BMI, blood chemistry (glucose and lipoprotein levels) and the use of cardiovascular medications are useful in clinical decision making. These pre-exercise test variables improved the predictive value of the GXT's in our sample.

Hypothermia enhances bcl-2 expression and protects against oxidative stress-induced cell death in Chinese hamster ovary cells.

Oxidative stress is one of the major causes of cellular injury. Various reactive oxygen (ROS) and nitrogen (RNS) species such as superoxide, hydroxyl radical, peroxynitrite, and nitric oxide are involved in the manifestations of different types of organ toxicity and the resultant syndromes, symptoms, or diseases. Hypothermic conditions have been reported to reduce the oxidative stress in various in vitro and in vivo studies. In the present study, we sought to determine the effect of lowered temperatures on oxidative stress-induced cell death in Chinese hamster ovary (CHO) cells. We also investigated the oxidative stress-induced alterations in the expression of anti-apoptotic protein, bcl-2, in CHO cells at lowered temperatures. CHO cells were incubated at four different temperatures of 30, 32, 35, and 37 degrees C (control temperature) from 1 to 4 d. In another set, the cells were incubated with 100 microM hydrogen peroxide (H(2)O(2)) for 30 min before harvesting at different time points. The cells were harvested at 1, 2, 3, and 4 d. Cell survival was significantly higher at 30 degrees C as compared to 37 degrees C over 4 d of incubation. In cells incubated with H(2)O(2), significantly higher cell viability was observed at lower temperatures as compared to the cells incubated at 37 degrees C. The activity of glutathione peroxidase (GSH-Px) also increased significantly at lower temperatures. Lowered temperature also provided a significant increase in the expression of anti-apoptotic protein, bcl-2 after 4 d of incubation. These data suggest that hypothermic conditions lowers the risk of oxidative stress-induced cellular damage and programmed cell death by increasing the activity of GSH-Px and by the induction in the expression of the anti-apoptotic protein, bcl-2.

Gastric intramural PCO2 during peritonitis and shock.

OBJECTIVE: To define whether increases in gastric intramural tissue CO2 and H+ increase during experimentally induced peritonitis with circulatory shock as they do under conditions of hemorrhagic shock and cardiac arrest. DESIGN AND SETTING: Peritonitis was induced in Sprague-Dawley rats by cecal ligation and fecal spillage. MEASUREMENTS AND RESULTS: Over an interval of 260 +/- 20 min in 5 animals, there was a progressive reduction in mean aortic pressure from 153 +/- 12 to 40 +/- 20 mm Hg and a decline in cardiac index from 429 +/- 135 to 178 +/- 7 ml/min. This was associated with increases in gastric intramural [H+] from 34 +/- 5 to 217 +/- 93 mmol/L (p = 0.001). Arterial blood lactate content concurrently increased from 0.9 +/- 0.1 to 4.6 +/- 0.7 mmol/L (p = 0.001). Only a late increase in gastric intramural PCO2 from 45 +/- 5 to 128 +/- 38 mm Hg (p = 0.01) was observed. CONCLUSION: In contrast to the gastric acid base changes that accompany hemorrhagic shock, in which there is an early and prominent increase in both PCO2 and [H+] in close relationship to decreases in cardiac output and arterial pressure, there was a prominent increase in gastric [H+] but only a delayed rise in gastric intramural PCO2. Arterial blood lactate and central venous oxygen saturation were earlier indicators of perfusion failure. Since the bicarbonate concentration in the stomach wall was substantially greater than that of simultaneously measured arterial blood, this has bearing on the current clinical method of gastric tonometry which assumes that arterial blood bicarbonate is equivalent to gastric wall bicarbonate.

Impaired glutathione peroxidase activity accounts for the age-related accumulation of hydrogen peroxide in activated human neutrophils.

BACKGROUND: As assessed by flow cytometry, the increase in hydrogen peroxide in individual neutrophils from old volunteers was significantly greater than in neutrophils from young volunteers. To explain the discrepancy in previous reports that showed reduced superoxide generation with age and our finding, we measured the kinetics of antioxidative enzymes. METHODS: Neutrophils were obtained from young (ages 21-34) and old (ages over 65) volunteers. The increase in hydrogen peroxide following stimulation with formyl peptide in individual neutrophils was assessed by flow cytometry by using dihydrorhodamine 123. The enzyme kinetics was determined from the best fit curve using Michaelis-Menten equations. RESULTS: Aging was associated with a significant reduction in the Vmax for glutathione peroxidase. The decreased activity was not due to selenium deficiency as the serum and neutrophil concentrations were identical with age. Following activation, a significant increase in the Km was noted in neutrophils from young but not from old volunteers. CONCLUSIONS: These results account for the increased intracellular accumulation of hydrogen peroxide as a function of age in stimulated neutrophils. These results provide evidence in humans of an age-related impairment in antioxidative defense mechanisms that support the free radical theory of aging.

MPP(+)-induced neurotoxicity in mouse is age-dependent: evidenced by the selective inhibition of complexes of electron transport.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been demonstrated to cause selective neurotoxicity by inhibiting complex I in mitochondria, through its toxic metabolite 1-methyl-4-phenylpyridine (MPP+) which is formed during the bioactivation of MPTP by monoamine oxidase B. In this report, we have evaluated the effect of MPP+ on the 4 mitochondrial respiratory chain complexes by incubating brain mitochondria of mice at 3 different age groups with MPP+ (200 microM) and monitoring enzyme activities of complexes I, II, III, and IV at 5, 10, 15, 30, 60, and 120 min. Complexes I, III, and IV showed significant inhibition within 15 min in all the age groups studied, followed by some recovery in enzyme activities upon further incubation for complexes I and IV. However, complex II was not affected by MPP+ at any age. Our data suggest that inhibition of complexes I, III, and IV by MPP+ efficiently restrict the transport of electrons down the respiratory chain which ultimately leads to decreased ATP production. This could further aggravate oxidative stress as ATP is required for the synthesis of glutathione (GSH), one of the important scavengers of free radicals. In this study, inhibition was more severe in mitochondrial preparations from older rather than younger mice. Additionally, young animals showed faster recovery following inhibition than old animals for complex I. Impaired respiratory chain function in older animals compared to younger ones supports the hypothesis of accumulation of age-related mitochondrial DNA mutations which partly encode for subunits of complexes I, III, and IV. From this study, it seems that inhibition of complexes I, III, and IV may be the underlying cause of neurotoxicity due to MPP+ which could be intensified by age-associated dysfunction of electron transport.

Perfusion of the subfoveal choriocapillaris affects visual recovery after submacular surgery in presumed ocular histoplasmosis syndrome.

PURPOSE: To determine the relationship between the visual result and perfusion of the subfoveal choriocapillaris after surgical excision of subfoveal neovascularization in presumed ocular histoplasmosis syndrome. METHODS: We reviewed the records of 38 eyes of 37 patients with gradable postoperative fluorescein angiograms and color photographs after surgical excision of a subfoveal neovascular membrane in presumed ocular histoplasmosis syndrome. The postoperative photographs and fluorescein angiograms were graded in a masked fashion for the presence of perfusion of the subfoveal choriocapillaris. We used preoperative and postoperative best-corrected visual acuities to determine the correlation between postoperative perfusion of the subfoveal choriocapillaris and both final visual acuity and visual improvement after surgery. RESULTS: After surgery, the subfoveal choriocapillaris was perfused in 24 of the 38 eyes (63%) and nonperfused in 14 (37%). Best-corrected visual acuity improved by at least 2 Snellen lines in 17 of the 24 perfused eyes (71%) and two of the 14 nonperfused eyes (14%) (P = .0089). Best-corrected visual acuity of 20/100 or better was achieved in 18 of the perfused eyes (75%) and four nonperfused eyes (29%) (P = .0076). CONCLUSION: Both final visual acuity and improvement in visual acuity were correlated with postoperative perfusion of the subfoveal choriocapillaris in patients with presumed occular histoplasmosis syndrome. Development of techniques to maintain or reestablish perfusion of the subfoveal choriocapillaris after surgery may improve visual outcome in these eyes.