Direct transfer of NADH between alpha-glycerol phosphate dehydrogenase and lactate dehydrogenase: fact or misinterpretation?

Following the criticism by Chock and Gutfreund [Chock, P.B. & Gutfreund, H. (1988) Proc. Natl. Acad. Sci. USA 85, 8870-8874], that our proposal of direct transfer of NADH between glycerol-3-phosphate dehydrogenase (alpha-glycerol phosphate dehydrogenase, alpha-GDH; EC 1.1.1.8) and L-lactate dehydrogenase (LDH; EC 1.1.1.27) was based on a misinterpretation of the kinetic data, we have reinvestigated the transfer mechanism between this enzyme pair. By using the "enzyme buffering" steady-state kinetic technique [Srivastava, D.K. & Bernhard, S.A. (1984) Biochemistry 23, 4538-4545], we examined the mechanism (random diffusion vs. direct transfer) of transfer of NADH between rabbit muscle alpha-GDH and pig heart LDH. The steady-state data reveal that the LDH-NADH complex and the alpha-GDH-NADH complex can serve as substrate for the alpha-GDH-catalyzed reaction and the LDH-catalyzed reaction, respectively. This is consistent with the direct-transfer mechanism and inconsistent with a mechanism in which free NADH is the only competent substrate for either enzyme-catalyzed reaction. The discrepancy between this conclusion and that of Chock and Gutfreund comes from (i) their incorrect measurement of the Km for NADH in the alpha-GDH-catalyzed reaction, (ii) inadequate design and range of the steady-state kinetic experiments, and (iii) their qualitative assessment of the prediction of the direct-transfer mechanism. Our transient kinetic measurements for the transfer of NADH from alpha-GDH to LDH and from LDH to alpha-GDH show that both are slower than predicted on the basis of free equilibration of NADH through the aqueous environment. The decrease in the rate of equilibration of NADH between alpha-GDH and LDH provides no support for the random-diffusion mechanism; rather, it suggests a direct interaction between enzymes that modulates the transfer rate of NADH. Thus, contrary to Chock and Gutfreund's conclusion, all our experimental data compel us to propose, once again, that NADH is transferred directly between the sites of alpha-GDH and LDH.     

Increased serum lactate dehydrogenase isoenzymes in Ph-negative chronic myeloproliferative diseases: a metabolic adaptation?

We evaluated the significance of lactate dehydrogenase (LDH) isoenzymes in chronic myeloproliferative disorders (CMDs) by studying LDH isoenzymes in the serum of patients with secondary polycythemia (SP), polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) in different disease status. LDH activity and isoenzymes were evaluated retrospectively in serum samples from four groups of patients and compared with a control group. LDH activity and isoenzyme distributions of patients with SP and PV did not reveal significant variations with respect to controls. In the ET and IMF group LDH isoenzyme revealed significant variations: IMF showed significant increase of LDH2 and significant reduction of LDH5 isoenzyme, whereas ET showed significant decrease in LDH1 and increase of LDH3. These data suggest that LDH isoenzyme patterns may be a useful marker of CMDs, but this enzymatic pattern could be expression of a metabolic adaptation.     

Who is not using condoms among HIV-positive patients in treatment in the largest city in Brazil?

Data on risky sexual behaviors in people living with HIV/AIDS (PLWHA) is still scarce in some populations around the world. The purpose of this study was to assess the factors associated with the use of condoms in a representative sample of PLWHA in outpatient treatment in the city of São Paulo. Six hundred and sixty-seven HIV-positive patients (383 men and 284 women) who were being treated at eight centers participated in this study. Data were collected using a sociodemographic survey, the Beck depression and anxiety inventories, a survey of alcohol and other drugs use, the Alcohol Use Disorders Identification Test, a sexual behavior survey, and the Sexual Risk Behavior Assessment Schedule. The majority of study participants were sexually active (almost 62% of the sample had at least one sexual partner in the last three months), and at least one-fourth engaged in unsafe sex (25.3% did not use condoms during at least one instance of anal and/or vaginal intercourse in the past three months). Multivariate logistic regression showed that engaging in unprotected sex was more likely among females (p < .001), persons with an HIV-positive partner (p < .001), and people using cannabis before sex (p = .002). These findings should stimulate health-care workers to create specific groups for women, seroconcordant couples, and cannabis users to discuss condom use, as they seem to be vulnerable groups.     

Echocardiographic patterns in treatment-na?ve HIV-positive patients in Lagos,south-west Nigeria

Introduction

Cardiovascular abnormalities are common in HIV-infected patients, although often clinically quiescent. This study sought to identify by echocardiography early abnormalities in treatment-naïve patients.

Methods

One hundred patients and 50 controls with no known traditional risk factors for cardiovascular disease were recruited for the study. The cases and controls were matched for age, gender and body mass index. Both groups had clinical and echocardiographic evaluation for cardiac abnormalities, and CD₄ count was measured in all patients.

Results

The cases comprised 57 females (57.0%) and 43 males (43.0%), while the controls were 28 females (56.0%) and 22 males (44.0%) (χ² = 0.01; p = 0.913). The mean age of the cases was 33.2 ± 7.7, while that of the controls was 31.7 ± 9.7 (t = 1.02; p = 0.31). Echocardiographic abnormalities were significantly more common in the cases than the controls (78 vs 16%; p = 0.000), including systolic dysfunction (30 vs 8%; p = 0.024) and diastolic dysfunction (32 vs 8%; p = 0.002). Other abnormalities noted in the cases were pericardial effusion in 47% (χ² = 32.10; p = 0.000) and dilated cardiomyopathy in 5% (five); none of the controls had either complication. One patient each had aortic root dilatation, mitral valve prolapse and isolated right heart dilatation and dysfunction.

Conclusion

Cardiac abnormalities are more common in HIV-infected people than in normal controls. A careful initial and periodic cardiac evaluation to detect early involvement of the heart in the HIV disease is recommended.     

An ultrasound-based comparative study on carotid plaques in HIV-positive patients vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory lesions?

BACKGROUND: We have previously described two cases of HIV-1-positive patients undergoing surgery for stenosis of the internal carotid arteries. Histology revealed an extensive inflammatory infiltration of the vascular wall and no evidence of atheromasic plaque. This unexpected pattern of carotid damage prompted us to perform a more accurate investigation of the characteristics of carotid plaques in a group of HIV-positive patients. The results were compared with those obtained from young patients affected by atherosclerosis of the epi-aortic vessels and patients with arteritis. METHODS: The patients underwent ultrasonography of the epi-aortic vessels using one of the latest generation power color-Doppler with 7.5 MHz probes. RESULTS: The study population included 61 HIV-positive patients and 47 HIV-negative patients (37 atherosclerotic and 10 with arteritis). Compared with HIV-negative atherosclerotic patients, there were significantly higher proportions of HIV-positive patients with iso-hypoechogenic lesions (81.8 vs. 29%) that were homogeneous both in their parietal and endoluminal portions (96.7 vs. 21.6% and 88.5 vs. 54.0%, respectively), with a smooth or slightly irregular surface (99.0 vs. 56.7%) (P=0.001 for all differences). No statistically significant differences were seen between HIV-positive and arteritis patients. CONCLUSION: Our study evidenced that the ultrasonographic structure of the epi-aortic lesions in HIV-positive patients substantially differ from those of the plaques in atherosclerotic patients, although they share similar characteristics with patients affected by arteritis. Further investigations are warranted to better define the structure and the mechanism of onset of these lesions.     

Familial Mediterranean Fever and Acute Rheumatic Fever: A Pathogenetic Relationship?

The frequency of acute rheumatic fever (ARF) in patients with familial Mediterranean fever (FMF) was documented and the effects of preceding streptococcal infections on the exacerbation of FMF were determined. In the first part of the study, 162 individuals with FMF were investigated for a history of ARF in a retrospective study. In the second part of the study, antistreptolysin-O (ASO) titres were measured in 130 individuals with FMF. Thirty-six patients had an arthritic attack (group A1), 55 patients had a typical FMF attack without arthritis (group A2) and 39 patients were in the attack-free interval (group B) during the investigation. Nine patients with FMF (5.5%) were considered to have ARF and three of them (1.85%) also had rheumatic heart disease. This prevalence of rheumatic heart disease in FMF is higher than that of the normal population (0.65%) reported in Turkey. Elevated ASO titres were found in 75%, 42% and 38% of the patients in groups A1, A2 and B, respectively. These percentages were found to be significantly higher in group A1 than in both groups A2 (p<0.01) and B (p<0.01). We concluded that patients with FMF might be more prone to the late complications of streptococcal infections. Received: 8 February 1999 / Accepted: 26 April 1999     

Treatment and prognosis of breast cancer in elderly: Different from young patients?

PurposeThe incidence of breast cancer increases with advanced age; 80% of patients are older then 50 years and 40% of patients are older then 65 years. But clinical trials including elderly patient are unsatisfactory. Most of the treatment decisions are based on retrospective subgroup analysis and extrapolations from studies including young patients. In this trial we aimed to reevaluate our elderly breast cancer patients’ data.MethodsThis study includes breast cancer patients age older then 65 years and treated at Cumhuriyet University Faculty of Medicine Medical Oncology Department. The patients’ data were reviewed retrospectively.ResultsSeventy-nine patient's data, who had treated and followed up at our institution were evaluated. Seventy-one (89.9%) patients were non-metastatic at the time of diagnosis. Chemotherapy and/or radiotherapy related side effects had detected in 66.6% of patients. The only grade 4 side effect was skin reaction in 1 patient. During the follow up period progression had developed at 100% of metastatic patients. In non-metastatic group, 2 patients (2.7%) had local relapse and 12 patients (16.6%) had distant metastasis.ConclusionElderly patients have more favorable prognostic factors from younger patients but their survival is not as good as expected. Chemotherapy or radiotherapy is not more toxic in elderly patients. So with close follow up elderly breast cancer patients should be treated as younger patients.     

Does functional recovery in elderly hip fracture patients differ between patients admitted from long-term care and the community?

BACKGROUND: It is largely unknown whether functional recovery following hip fracture differs between long-term care (LTC) and community-dwelling residents. Our primary purpose was to compare recovery between these patients 6 months following hip fracture, controlling for known prognostic factors. Secondarily, we examined the contribution of residential status, in addition to patient characteristics, to functional recovery. METHODS: We studied a population-based inception cohort of 451 hip fracture patients >/= 65 years old admitted to one Canadian health region hospital between July 1999 and September 2000. Participants completed the Modified Barthel Functional Index (MBI) in hospital and again via telephone interviews 6 months postoperatively. Data were also collected on surgery and rehabilitation timing, length of hospital stay (LOS). and discharge destination. Relative change from prefracture function adjusting for known prognostic factors, and the proportion of participants returning to prefracture function were compared between the LTC and community-dwelling residents. RESULTS: LTC residents (n = 115) were older, with lower function prefracture, more comorbidities, and increased dementia than community-dwelling residents (n = 336). Six months postfracture, 17 (22%) LTC and 180 (71%) community-dwelling residents had regained prefracture function (p <.001). LTC residents had 33% lower (-40.6, -27.2) and community-dwelling residents 11.6% lower (-14.8, -8.4) 6-month MBI scores relative to prefracture scores after risk adjustment. Residential status was significantly associated with risk-adjusted functional recovery (p <.001). Median LOS was 4 days less for LTC than for community-dwelling residents (p <.001). Twelve (10%) LTC and 266 (79%) community-dwelling residents were discharged to inpatient rehabilitation (p <.001). CONCLUSION: Following hip fracture, most LTC residents do not regain prefracture function irrespective of known prognostic factors. Further investigation is needed as to the extent to which personal and environmental characteristics contribute to outcome after hip fracture.     

Cotton Fever: Does the Patient Know Best?

Fever and leukocytosis have many possible etiologies in injection drug users. We present a case of a 22-year-old woman with fever and leukocytosis that were presumed secondary to cotton fever, a rarely recognized complication of injection drug use, after an extensive workup. Cotton fever is a benign, self-limited febrile syndrome characterized by fevers, leukocytosis, myalgias, nausea and vomiting, occurring in injection drug users who filter their drug suspensions through cotton balls. While this syndrome is commonly recognized amongst the injection drug user population, there is a paucity of data in the medical literature. We review the case presentation and available literature related to cotton fever.     

Renal function and delirium in older fracture patients: different information from different formulas?

Objectivesthe association between renal function and delirium has not been investigated in older fracture patients. Creatinine is frequently low in these subjects, which may influence the association between delirium and renal function as estimated with creatinine-based formulas. Cystatin C could be a more reliable filtration marker in these patients.Aimto confirm the association between renal function and delirium in older fracture patients comparing creatinine- and cystatin-based estimated glomerular filtration rate (eGFR)Methodspatients aged 65+ requiring surgery for traumatic bone fractures were included. Six equations were used to calculate eGFR, based on serum creatinine and/or cystatin C obtained within 24 h of admission: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPI_cr, CKD-EPI_cys, CKD-EPI_cr-cys) and Berlin Initiative Study equations (BIS-1, BIS-2). Delirium was identified with a chart-based method.Results571 patients (mean age 83) were enrolled. Delirium occurred in the 34% and was associated with a lower eGFR regardless of the equation used. In a multivariable model, the association between moderate renal impairment (eGFR 30–60 ml/min/1.73 m²) and delirium remained significant in patients aged 75–84 and only when estimated with cystatin-based or BIS-1 equations. Only dementia was significantly associated with delirium in subjects 85+.Conclusionsin older fracture patients, moderate renal impairment was independently associated with delirium only among subjects aged 75–84, when eGFR was estimated with cystatin-based or BIS 1 equations, and not with the most commonly used equations (MDRD, CKD-EPI_cr).