Synchronous fluctuations of blood insulin and lactate concentrations in humans

Diseases associated with pathological fibroproliferation represent a major cause of morbidity and mortality. Despite the importance of this class of disorders, current therapy is of limited value, and no therapy is available to reduce the fibroblast population size within existing fibrotic lesions. In this regard, constitutive expression of growth-promoting genes can sensitize cells to undergo apoptosis. Studies in our laboratory have demonstrated that lovastatin potently induces apoptosis in fibroblasts constitutively expressing Myc, and that lung fibroblasts isolated from fibrotic lesions constitutively express growth-promoting genes. In this study, we sought to determine if nontransformed lung fibroblasts would manifest susceptibility to lovastatin-induced apoptosis similar to that observed in fibroblasts ectopically expressing Myc. Here we show that clinically achievable concentrations of lovastatin induce apoptosis in normal and fibrotic lung fibroblasts in vitro, as evidenced by acridine orange staining, terminal transferase nick end translation (TUNEL), and DNA laddering. Apoptosis of human lung fibroblasts was dose- and time-dependent, and blocked by exogenous mevalonic acid. Furthermore, apoptosis was associated with decreased levels of mature Ras, a molecule directly implicated in fibroblast rescue from apoptosis. The ability of lovastatin to induce fibroblast apoptosis in vivo was examined using a guinea pig wound chamber model. Lovastatin (5 microM, 8 d) reduced granulation tissue formation in the wound chambers by 64.7%, with associated ultrastructural evidence of fibroblast apoptosis. These findings support further study of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors as potential therapy for patients with fibroproliferative disorders.     

Capillary blood lactate concentrations during intermittent all-out exercise

Struma has called for treatment very early in medical history due to its appearance. At the beginning of our calendar, the physicians dealt with this problem already. This paper gives a historical review about the surgical treatment of struma.     

Plasma endothelin 1 concentrations in children with congenital heart defects

A therapy refractory brain edema is causally responsible for the death of approximately 50% of patients following severe craniocerebral trauma. The development of a brain edema which cannot be controlled by conservative means is also the most frequent cause of death with cerebral emergencies not caused by trauma. The cerebral perfusion pressure (CPP), which is the decisive factor for sufficient cerebral oxygenation, can be calculated on condition that the mean arterial pressure (MAP) and the intracranial pressure (ICP) are continually monitored: (CPP = MAP-ICP). On the basis of neurological observations, the computer tomographical results and the jugular vein oxymetry, an incipient cerebral decompensation and consequently the failure of the ongoing conservative treatment becomes apparent at an early stage. At this point at the latest, a bitemporal craniectomy should be considered for treatment. A drop in CPP to below 70 mmHg for adults and 50 mmHg for children is regarded as the intervention limits. Our experience shows that the outcome can be improved if the time of the bitemporal craniectomy lies before that of the cerebral decompensation.     

Plasma and blood vessel endothelin-1 concentrations in hypertensive uremic rats treated with erythropoietin

The present study was designed to evaluate whether changes in plasma and blood vessel endothelin-1 (ET-1) concentrations may play a role in the enhanced blood pressure response to recombinant human erythropoietin (r-HuEPO) replacement therapy in uremia. Renal failure was induced by 5/6 nephrectomy (Nx). Uremic rats received either r-HuEPO (100 u s.c. three times a week) or the vehicle for 5 weeks. They were compared to control rats receiving the vehicle. Systolic blood pressure (tail cuff method), hematocrit, serum creatinine, plasma and tissue ET-1 were measured at the end of the protocol. Immunoreactive ET-1 (ir-ET-1) was determined by radioimmunoassay of acid-extracts from the plasma, thoracic aorta and mesenteric arterial bed. Creatinine increased about three fold in Nx animals. Blood pressure in control rats was 120+/-3 mmHg compared to 161 +/-6 mmHg in the Nx + vehicle group (p <0.01) and 199+/-9 mmHg in the Nx + r-HuEPO group (p <0.01 vs Nx + vehicle). Hematocrit in control rats was 41.3+/-0.4% vs 32.6+/-1.8% in the Nx + vehicle group (p <0.01) and 47.6+/-1.5% in the Nx + r-HuEPO group (p <0.01). Plasma ir-ET-1 levels were similar in the Nx + vehicle and Nx + r-HuEPO groups (7.9+/-1.0 and 7.8+/-0.8 pg/ml). In contrast, thoracic aorta ir-ET-1 content was significantly higher in the Nx + r-HuEPO group than in the Nx + vehicle group (20.3+/-2.9 vs 13.4+/-1.9 pg, p <0.05). Similar results were obtained in the mesenteric arterial bed. There were significant correlations between blood pressure and ir-ET-1 content in the thoracic aorta (r= 0.45, p<0.05) and in the mesenteric arterial bed (r= 0.41, p<0.05). Vascular ET-1 content but not plasma levels are increased in uremic rats treated with r-HuEPO suggesting an increase in blood vessel ET-1 production which may play a role in the pathogenesis of r-HuEPO-induced hypertension.     

Plasma cyclic AMP and blood lactate responses to incremental cycling in untrained male subjects

Recently, it has been suggested that epinephrine influences blood lactate and the lactate threshold during incremental exercise through a beta-adrenergic adenylate cyclase dependent mechanism. We sought to characterize the relationship between the changes in the beta-adrenergic adenylate cyclase system and blood lactate during incremental exercise indirectly through the measurement of plasma cAMP. The relationships of plasma cAMP to blood lactate levels and the lactate threshold were examined in nine untrained male subjects. Each subject performed an incremental exercise test to volitional exhaustion on an electronically-braked cycle ergometer. Although plasma cAMP was rising at the lactate threshold, it did not demonstrate the classic threshold response usually seen in blood lactate. Pairwise matched t-tests were used as a post-hoc test to determine if the successive changes in blood lactate and plasma cAMP between 21.4, 38.6, 58.7, 81.2 and 100% of VO2max were significant. Plasma cAMP was rising between 38.6% and 58.7% and between 58.7% and 81.2% of VO2max, but these changes in plasma cAMP did not reach statistical significance (p > 0.0125) with Bonferoni adjustment. The change in plasma cAMP compared to its previous value as well as the change in plasma cAMP above the resting value was not statistically significant until 81.2% of VO2max. A moderate but significant correlation was observed between blood lactate and plasma cAMP levels (r = 0.612) using blood samples obtained at each workstage in all subjects. The mean correlation between blood lactate and plasma cAMP was 0.75 (S.E. = 0.05) and ranged between 0.58 and 0.97 in individual subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated blood lead levels in children are associated with lower erythropoietin concentrations

PURPOSE: We investigated the incidence of well-directed violent behavior and suicide attempts in patients with temporal lobe epilepsy, with special attention to postictal psychosis. METHODS: We compared 57 episodes of postictal psychosis with 62 episodes of acute interictal (or alternative) psychosis and with 134 complex partial seizures. All patients were matched for age and for age at onset of seizures. RESULTS: The incidence of well-directed violent behavior against human beings was significantly higher (23%) during postictal psychotic episodes than during acute interictal episodes (5%) and postictal confusion (1%). Suicide attempts were also more frequent during postictal psychosis (7%) than during either acute interictal psychosis (2%) or postictal confusion (0%). CONCLUSIONS: Our study showed that well-directed violent and self-destructive behavior was not a feature of epileptic psychosis in general but a specific hallmark of postictal psychosis.     

Prevalence and age-specific incidence of burns in Ghanaian children

The incidence of burns in developing countries is not precisely known due to unavailability or incompleteness of death registration and disease reporting. In this study, we determined prevalence and age-specific incidence of burns in children 0-5 years in the Ashanti region of Ghana using burn scars as proxy. We used a community-based, multi-site survey to identify children who had scars as evidence of previous burns. A scar prevalence of 6 per cent was found. No sex differences were found. However, significant differences were found among age groups, with children aged 18-23 months having the highest incidence (57.4 per 1000 person-years). There was evidence of focal occurrence of childhood burns in certain districts, and a higher prevalence in rural areas. We conclude that childhood burns are a significant health problem in Ghana, especially among rural residents and the very young, and recommend that interventions be developed to control them.     

Plasma concentrations of bupivacaine for continuous peridural anesthesia in children]

BACKGROUND: Supraclinoid carotid aneurysms have traditionally been classified according to their relation to the major carotid branches, but considerable variation exists with respect to site of origin, projection, and relationship to the skull base. Distal internal carotid aneurysms with a superior or medial projection are uncommon vascular lesions, with an unusually high incidence of operative complications. METHODS: Surgical experience with five patients suffering from subarachnoid hemorrhage due to ruptured aneurysms of the dorsomedial wall of the distal internal carotid artery is presented, with emphasis on their angiographic appearance, anatomical features, and operative management. RESULTS: All five patients underwent surgical clipping. Intra-operative rupture occurred in two cases, with avulsion of the aneurysm from the internal carotid artery in both. A third patient experienced recurrent subarachnoid hemorrhage three days after uneventful surgery, due to the clip shearing off of the parent vessel. CONCLUSIONS: Distal internal carotid aneurysms do not conform to the usual principles of aneurysm formation and are unique in their dorsomedial location unrelated to an arterial bifurcation. Although their anatomy is straightforward and exposure is not restricted by bone or dural structures of the skull base, they possess extremely fragile necks which make surgical management particularly hazardous.     

Front-door concentrations and personal exposures of Danish children to nitrogen dioxide

The aims of the study were to evaluate the front-door concentration of traffic exhaust fumes as a surrogate for the personal exposure of children and to study factors in the behavior and the environment of children that affect their personal exposure to nitrogen dioxide (NO(2)). The exposure to NO(2) of 103 children living in Copenhagen and 101 children living in rural areas of Denmark was studied by measuring average concentrations over 1 week with diffusive badge samplers placed outside the front door of the home, inside the child's bedroom, and on each child. Detailed information about the activities of the children involving potential exposure to NO(2) was noted in diaries. The results indicated that the front-door concentration of traffic pollution might be used to classify the personal exposure of urban children, although misclassification would be introduced. Multiple regression analysis showed several factors that affected the personal NO(2) exposure of the children independently, including the front-door concentration, the bedroom concentration, time spent outdoors, gas appliances used at home, passive smoking, and burning candles.     

Concentration of nitrogen oxides in fuel-combustion products

Methods of predicting the formation of nitrogen oxides in the combustion products of gaseous fuel are considered. Predicted concentrations of nitrogen oxides in the smoke gases are obtained for the combustion of natural gas in burners with different methods of mixing the fuel and air. Other conditions being equal, the minimum content of nitrogen oxides in the combustion products is seen in burners with open flames (flat-flame burners and radiant burners) and in burners with improved mixing. The content of nitrogen oxides is somewhat higher in burners without preliminary mixing of the fuel and air. The most toxic smoke gases are formed in injection burners. On heating the air for combustion, the content of nitrogen oxides in the smoke gases increases by a factor of 2–3. The discrepancy between the results obtained by the methods considered is 5–7% for high-temperature furnaces and 20% or more for low-temperature furnaces. With considerable air heating, the discrepancy increases.     

Plasma and blood lead concentrations, lead absorption, and lead excretion in nonhuman primates

The effects of pH, temperature, block of energy production, calcium/calmodulin, protein phosphorylation, and cytoskeleton-disrupting agents (cytochalasin D, nocodazole) on the integrity of the membrane skeleton were studied in polarized MDCK cells. The intracellular distributions of alpha-fodrin, actin, and ankyrin were monitored by immunofluorescence microscopy. The membrane skeleton, once assembled, seemed to be quite stable; the only factors releasing alpha-fodrin from the lateral walls were the acidification of the cytoplasm and the depletion of extracellular calcium ions. Upon cellular acidification, some actin was also released from its normal location along the lateral walls and was seen in colocalization with alpha-fodrin in the cytoplasm, whereas ankyrin remained associated with the lateral walls. No accumulation of plasma membrane lipids was observed in the cytoplasm of acidified cells, as visualized by TMA-DPH. These results suggest that the linkages between the fodrin-actin complex and its membrane association sites are broken upon acidification. The pH-induced change in alpha-fodrin localization was reversible upon restoring the normal pH. Reassembly of the membrane skeleton, however, required temperatures above +20 degrees C, normal energy production, proper cell-cell contacts, and polymerized actin. Release of alpha-fodrin from the lateral walls to the cytoplasm was also observed upon depletion of extracellular calcium ions. This change was accompanied by the disruption of cell-cell contacts, supporting the role of proper cell-cell contacts in the maintenance of the membrane skeleton polarity. These results suggest that local alterations of the cytoplasmic pH and calcium ion concentration may be important in regulating the integrity of the membrane skeleton.     

Plasma endotoxin and cytokine concentrations in patients with hemorrhagic shock

OBJECTIVES: The roles of cytokines and endotoxin in hemorrhagic shock, particularly the translocation of endotoxin and bacteria during hemorrhagic shock, were investigated. DESIGN: Prospective study. SETTING: Critical care and emergency center of a university hospital. PATIENTS: Twenty-nine patients with hemorrhagic shock and 20 healthy controls. INTERVENTIONS: Serial blood samples were collected from both study and control patients. Standard resuscitation techniques were used. MEASUREMENTS AND MAIN RESULTS: Plasma levels of endotoxin and various cytokines were determined repeatedly during hemorrhagic shock. Endotoxin was measured using an endotoxin-specific assay in addition to a new perchloric acid method for pretreatment of plasma. Cytokines were measured by commercial enzyme-linked immunosorbent assays. Plasma endotoxin concentrations remained within the normal range for 7 days after admission. Although levels of tumor necrosis factor-alpha and several interleukins increased slightly in some patients, these cytokines did not reach the levels seen in septic shock. CONCLUSIONS: Translocation of bacteria or endotoxin from the gastrointestinal tract into the bloodstream has been noted in animal experiments; however, translocation was not detected in our patients with hemorrhagic shock.     

Quinine pharmacokinetics in young children with severe malaria

In this study, we determined selenium concentrations in serum samples of healthy women (146 pregnant and 74 nonpregnant) living in the Mediterranean area of the coast of Granada (southeast Spain). The subjects were distributed in two groups: group A (pregnant women), divided into three categories according to the trimester of pregnancy, and group B (nonpregnant women). No significant differences were observed in the selenium levels either among pregnant women according to the trimester of pregnancy or in the group of nonpregnant women. No other significant differences were determined as regards the age of pregnant women (P > 0.05). Serum selenium levels are slightly lower during pregnancy. Considering that serum selenium levels affect the body selenium status, the concentrations determined establish the non-existence of selenium problems in the daily dietary intake with respect to maternal and fetal necessities during pregnancy.     

Blood lactate concentrations during incremental exercise in subjects with sickle cell trait

The need for lateral release or "venting" of the A2 and A4 pulleys either to facilitate repair of the flexor tendon(s) or to allow free gliding of the repair(s) was examined in 126 consecutive zone 2 flexor tendon injuries within the tendon sheath and distal to the distal edge of the A2 pulley (zones 2A and 2B of Tang's classification) in which at least one flexor tendon had been completely divided. This study showed that 81 (64%) of these repairs required venting of one or the other pulley. It was necessary to vent the A4 pulley between 10 and 100% of its length in 71 (56%) of the fingers and to vent the distal edge of the A2 pulley by 4 to 10 mm in 10 (8%) of the fingers.     

Plasma homocysteine concentrations in patients with type 1 diabetes

OBJECTIVE: To determine the plasma concentration of total homocysteine (tHcy), a recognized risk factor for vascular disease, in patients with type 1 diabetes and to examine the relationships with age, sex, duration of diabetes, microvascular complications and neuropathy, and folic acid concentration. RESEARCH DESIGN AND METHODS: Plasma tHcy and folic acid concentrations were measured in a randomly selected cohort of type 1 diabetic patients (n = 119), well characterized as regards microvascular complications, and in a matched control group (n = 51). RESULTS: Plasma tHcy was higher in male than in female control subjects (geometric mean [95% CI]: 9.3 [8.0-10.9] vs. 6.1 [5.2-7.2] micromol/l, P < 0.001), as previously described, but there was no sex difference in diabetic patients. Plasma tHcy significantly correlated with age in patients (r = 0.348, P < 0.01) but not in control subjects (r = 0.007, P = 0.96). Male patients without microvascular complications had lower plasma tHcy concentrations than did male control subjects (6.2 [5.1-7.5] vs. 9.3 [8.0-10.9] micromol/l, P < 0.001), but values in female patients without complications were similar to those of female control subjects. Plasma folic acid concentration was higher in diabetic patients than in control subjects. The expected negative association between plasma tHcy and folic acid was stronger in control subjects than in patients. CONCLUSIONS: Subnormal tHcy concentrations in male patients, the absence of a sex difference, and the positive association with age indicate that homocysteine metabolism differs between type 1 diabetic patients and control subjects. Homocysteine is unlikely to be of pathogenic significance in patients, particularly male subjects, with early microvascular disease and/or neuropathy.     

Comparison of heroin and cocaine concentrations in saliva with concentrations in blood and plasma

Saliva is an alternate biological matrix for drug testing that has several advantages over more traditional fluids such as blood and urine. Collection is rapid, noninvasive, and relatively easy to obtain. Several reports have detailed the appearance of drugs of abuse in saliva, but few have compared the excretion profiles of drugs administered by different routes. In this study, subjects were administered three smoked and three intravenous doses of heroin in an ascending dose design. Blood and saliva were collected periodically after drug administration and analyzed by gas chromatography-mass spectrometry (GC-MS) for heroin, 6-acetylmorphine, and morphine. In a second study, subjects were administered a single, smoked dose of 40 mg cocaine base and an intravenous dose of 44.8 mg cocaine HO on separate occasions. Plasma and saliva were collected and analyzed by CC-MS for cocaine, anhydroecgonine methyl ester (AEME), and seven additional metabolites. Heroin and 6-acetylmorphine were detected in the first saliva sample collected (2 min) following drug administration by both routes. Peak heroin concentrations were achieved quickly, between 2 and 5 min after intravenous administration and at 2 min after smoke heroin. Peak heroin concentrations in saliva after smoking heroin base ranged from 3534 (2.6 mg) to 20,580 ng/mL (5.2 mg), and after intravenous administration, concentrations ranged from 6 (10 mg heroin HCl to 30 ng/mL (12 mg heroin HCl. Saliva concentrations of heroin declined rapidly after intravenous administration, reaching the limit of sensitivity of the assay (1 ng/mL) by 60 min. Heroin concentrations in saliva after smoking declined slowly; detection times ranged from 4 to 24 h. Cocaine was the major analyte detected in saliva and plasma after smoked and intravenous administration. Peak saliva cocaine concentrations after intravenous administration ranged from 428 to 1927 ng/mL (N = 7); after smoking, they ranged from 15,852 to 504,880 ng/mL (N = 7). Peak plasma cocaine concentrations after intravenous administration ranged from 122 to 442 ng/mL A = 7), and after smoking, concentrations ranged from 46 to 291 ng/mL A = 7). The thermal degradation product of cocaine, AEME, was detected in saliva but not in plasma after smoking. Peak saliva AEME concentrations were achieved at 2 min and ranged from 558 to 4374 ng/mL (N = 7). These are the first reported observations of heroin and metabolites in saliva following heroin smoking and of AEME in saliva after smoking cocaine base. The presence of AEME in saliva may be useful as a marker of the smoked route following cocaine administration.     

Enteric pathogens in severe forms of acute gastroenteritis in Ghanaian children

Diarrheal disease is the major cause of childhood morbidity in developing countries. Although malnutrition is known as a risk factor for severe gastroenteritis, the role of enteric pathogens in the clinical severity is unclear. The present study was conducted in well nourished Ghanaian preschool children during a 3 month period of the rainy season to assess the relationship between enteric pathogens and severe gastroenteritis. Two hundred and twenty-five children with acute gastroenteritis and 64 age-matched control children were prospectively examined for the severity of dehydration and enteric pathogens in their stools. Of the 225 children with gastroenteritis, 69.8% (157/225) had mild dehydration and 30.2% (68/225) had severe dehydration. Bacteria were similarly isolated in stool samples from children with mild and severe dehydration and controls. Rotavirus accounted for 20.6% of children with severe dehydration and was more often isolated in stools from patients with severe dehydration than those from controls. Furthermore, the mixed infections associated with rotavirus and bacteria were more often found in patients with severe dehydration than those with mild dehydration or controls. Parasites were similarly found at low incidences among the three groups. The present study implied that rotavirus was more responsible for severe gastroenteritis than bacteria or parasites. However, factors other than enteric pathogens must be sought in a considerable number of severe cases. A large scale study throughout a year is recommended to obtain more precise information that would reflect the seasonal variation of rotavirus infections.