Discrimination of normal and abnormal prothrombin and protein C in plasma using a calcium ion-inhibited monoclonal antibody to a common epitope on several vitamin K-dependent proteins

Vitamin K deficiency or administration of vitamin K antagonists results in the biosynthesis of abnormal des-gamma-carboxy forms of the vitamin K-dependent proteins. Monoclonal antibody H-11 binds several vitamin K- dependent proteins at a determinant that includes the first two residues of gamma-carboxyglutamic acid. Antibody H-11 binds fully carboxylated prothrombin and protein C in the presence of EDTA but binding is inhibited by the divalent metal ions, calcium, magnesium, and manganese. By contrast, des-gamma-carboxy prothrombin and protein C bind antibody H-11 the same in the presence of EDTA or calcium ion. Antibody H-11 thus appears to bind a conserved antigenic site containing gamma-carboxyglutamic acid that in the presence of divalent metal ion undergoes a conformational transition. This ability of antibody H-11 to bind des-gamma-carboxy prothrombin and protein C in the presence of calcium ion allowed the development of an immunoassay for these proteins in plasma. Prothrombin and protein C from stably anticoagulated individuals receiving warfarin were characterized by their ability to bind antibody H-11 in the presence of calcium ion. Binding of prothrombin and protein C to antibody H-11 in the presence of calcium correlated temporally with warfarin administration. The inability of calcium ion to inhibit binding of antibody H-11 to abnormal prothrombin and protein C in plasma suggests that the circulating forms of both proteins following warfarin administration cannot undergo the metal ion-dependent conformational transition that includes sequence residues 1 through 12.     

A clinical,randomized study on the influence of dental whitening on Streptococcus mutans population

Background

Dental whitening with peroxides has been popularized through the at‐home technique, which employs low concentrations of peroxide applied in individual trays. However, there are few clinical trials reporting the effects of its continuous use on oral microbiota. Thus, the purpose of the present clinical, randomized study was to evaluate the influence of at‐home whitening treatment on Streptococcus mutans in saliva, buccal mucosa, and subgingival and supragingival plaque.

Methods

Thirty volunteers were randomly divided into two study groups (N = 15) according to the whitening therapy: G CP, whitening using 10% carbamide peroxide 4 h daily for 21 days; and G HP, whitening using 6% hydrogen peroxide 1.5 h daily for 21 days. Samples from the predetermined locations were collected at three evaluation periods: T1, before; T2, immediately after; and T3, 30 days after the beginning of the treatment. The microbiological evaluation was made using conventional and molecular methods.

Results

Student's t‐test demonstrated a statistically significant decrease in S. mutans population in the subgingival and supragingival plaque for HP samples between T1 and T2 no difference was found between T1 and T3 regardless of the location and the whitening product used (α = 0.05).

Conclusions

Although HP reduced S. mutans during treatment, the levels returned to baseline when assessed 30 days after the treatment.     

Airway pressure and transpulmonary pressure during high-frequency oscillation for acute respiratory distress syndrome

High-frequency oscillation is a novel form of ventilation increasingly being used to treat refractory hypoxic respiratory failure resulting from acute lung injury or acute respiratory distress syndrome. Although there is no known relationship between airway pressure and transpulmonary pressure during conventional mechanical ventilation, no study has attempted to determine transpulmonary pressure during high-frequency oscillation.

BACKGROUND:

High-frequency oscillation (HFO) is used for the treatment of refractory hypoxic respiratory failure.

OBJECTIVE:

To demonstrate that the mean transpulmonary pressure (P_L) cannot be inferred from mean airway pressure (mPaw).

METHODS:

In seven patients already undergoing HFO for refractory acute respiratory distress syndrome, esophageal pressure (Pes) was measured using an esophageal balloon catheter. Pleural pressure (Ppl) and P_L were calculated from Pes.

MAIN RESULTS:

In the seven patients (mean [± SD] age 59±9 years) treated with HFO at 5±1 Hz and amplitude 75±10 cmH₂O, the mPaw was 27±6 cmH₂O, Ppl was 9±6 cmH₂O and P_L was 18±11 cmH₂O. Successful catheter placement and measurement of Pes occurred in 100% of subjects. There was no correlation between P_L and mPaw. The majority of subjects required hemodynamic support during the use of HFO; the frequency and degree of support during the study period was no different than that before the study.

CONCLUSION:

The present report is the first to describe measuring Pes and calculating Ppl during HFO for acute respiratory distress syndrome. While both current guidelines and recent trials have titrated treatment based on mPaw and oxygenation, there is wide variability in P_L during HFO and P_L cannot be predicted from mPaw.     

Recombinant human interleukin-6 induces a rapid and reversible anemia in cancer patients

Initial studies have shown that recombinant human interleukin-6 (rhIL- 6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II study. rhIL-6 was administered subcutaneously at 150 micrograms once daily for 6 consecutive weeks. Various hematologic and biochemical parameters were measured weekly during rhIL-6 treatment and 4 weeks after rhIL-6 discontinuation. To determine plasma volume and red blood cell (RBC) volume, radioisotope dilution assays with labeled autologous RBCs and with human serum albumin were performed before rhIL-6 administration and on day 8 of rhIL-6 therapy. Hemoglobin levels decreased (mean change +/- SE) 7% +/- 1.5% within 3 days after the start of rhIL-6 therapy (P < .0001) and 19% +/- 2% at week 4. Levels had normalized at follow-up. The plasma volume increased 18% +/- 5% during the first week of rhIL-6 administration (P < .003), whereas RBC volume remained unaffected. The mean RBC corpuscular volume remained unchanged for 2 weeks and then began to decrease slowly, reaching its nadir at week 6 (5% +/- 1%; P < .01). Serum iron levels decreased 65% +/- 12% at week 4 (P < .002) and then returned to initial baseline values. Erythropoietin levels increased rapidly up to 68% at week 3 (P < .0001) and had normalized 4 weeks after rhIL-6 therapy. Levels of serum albumin, prealbumin, and transferrin decreased (P < .0001, P < .003, and P < .0001, respectively), whereas levels of serum amyloid A (P < .003), C-reactive protein, haptoglobin, and alpha-1-antitrypsin (P < .0001) increased during rhIL-6 treatment. All levels returned to pretreatment values after discontinuation of rhIL-6. No alterations in reticulocyte counts, serum lactic dehydrogenase levels, and bilirubin levels were observed. A 6-week regimen of subcutaneous rhIL-6 results in a rapid dilution anemia, caused by an acute and significant increase in plasma volume and followed by hypoferremia. This anemia is reversible after the cessation of rhIL-6 treatment.     

Comparison of the Effect of Thiazide Diuretics and Other Antihypertensive Drugs on Central Blood Pressure: Cross‐Sectional Analysis Among Nondiabetic Patients

Thiazide diuretics (TDs) are a cost‐effective first‐line therapy for uncomplicated hypertension; however, they are less prescribed than other options. The authors aimed to assess the noninferiority of TDs relative to different classes of antihypertensive medications in relation to central blood pressure. Cross‐sectional data from the Quebec CARTaGENE project was used. Nondiabetic hypertensive participants on monotherapy for hypertension were studied. Separate adjusted models were constructed to establish noninferiority of TDs to non‐TD antihypertensive medications for central blood pressure measurements. Models included a set of potential confounders. Of the 1194 hypertensive participants, 7.4% were taking TDs. We found that TDs were comparable with non‐TD antihypertensive medications for central systolic blood pressure (adjusted regression coefficient, 0.45; 95% confidence interval, −1.61 to 2.50). No differences in other central measurements were noted. The results provide additional support that TDs are at least as effective as other first‐line medications for treating uncomplicated hypertension.

Elevated blood pressure (BP) is a well‐known predictor of cardiovascular risk and mortality and lowering BP is an effective means of reducing cardiovascular events.¹, ² Although lifestyle modification is important in the management of hypertension, most hypertensive patients require some level of pharmacologic treatment.³ The use of antihypertensive medication has remarkably increased in the past years. A large‐scale national survey documented that 77% of US adults with hypertension used at least one antihypertensive medication.⁴ In Canada, the implementation of the Canadian Hypertension Education Program (CHEP), which is responsible for the generation of the hypertension guidelines in Canada and their annual update, has resulted in improved diagnosis and management of hypertension in Canada.⁵, ⁶ In adults with hypertension without compelling indications for specific agents, existing guidelines emphasize that thiazide diuretics (TDs), when used as monotherapy, are as effective as calcium channel blockers (CCBs), angiotensin‐converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs), in lowering BP and preventing cardiovascular and renal endpoints.², ⁷ Some studies have shown measurements of central systolic BP (cSBP) and central pulse pressure (cPP) to be better predictors of target organ damage and cardiovascular disease than peripheral (brachial) systolic BP (pSBP) or peripheral pulse pressure (pPP).⁸, ⁹ When compared with peripheral BP (pBP), central BP (cBP) offers a more accurate estimation of the load imposed on the aorta and the left ventricle, and, in turn, of the overall vascular damage and prognosis.¹⁰, ¹¹ cBP can be measured noninvasively using pulse wave analysis (PWA), a technique based on applanation tonometry of the radial artery. PWA provides additional information, in particular the calculation of the augmentation index (AIx).¹² AIx represents wave reflection, and an indirect measure of arterial stiffness.In this study, we aimed to assess the noninferiority of TDs relative to different classes of antihypertensive medications in relation to cBP and AIx.     

Abnormalities of the neonatal brain: MR imaging. Part II. Hypoxic- ischemic brain injury

Eighty-five infants, 82 of whom were 29-44 weeks postconceptional age, were imaged with a 0.6-T magnet. Eight infants had cerebral infarction. In premature neonates with very water, low-intensity white matter on T1-weighted images, ultrasound was better than both computed tomography and magnetic resonance (MR) imaging in depicting parenchymal changes of infarction or edema. However, after 37 weeks gestation, MR imaging was superior. Cerebral atrophy, present in seven infants, was consistent with subarachnoid space widths of 7 mm or more, or subarachnoid space widths of 5-6 mm with ventricular/brain ratios of 0.36 or greater. Delayed myelination was seen in a total of 18 infants with histories of hypoxic-ischemic insult. MR imaging shows promise in the neonatal period. It facilitates recognition of infarcts in full-term infants and may be used to predict abnormal neurologic outcome in infants who have initial delayed myelination.     

Monitoring of the neonate undergoing MR imaging: technical considerations. Work in progress

Instrument monitoring of vital signs in neonates undergoing magnetic resonance (MR) imaging can be difficult because of the unique environmental restrictions imposed by the imager. The authors present their experience with monitoring more than 50 newborn infants and discuss the interaction of monitoring devices with the MR imager. Several MR-compatible monitors allow continuous evaluation of body temperature, heart rate, blood pressure, and auscultation of heart sounds and respiration in mechanically ventilated infants. Signal-to-noise (S/N) ratio measurements taken during imaging of the head of an infant with these monitors in place did not differ appreciably from the ratio obtained during imaging without monitors. Tip angles should be optimized to account for widely varying head size among neonates, since adverse monitoring effects are significantly compounded by improper tip angle adjustment.     

Spontaneous peritonitis caused by Leminorella grimontii

A case of spontaneous peritonitis caused by Leminorella grimontii in a 63-year-old man with cirrhosis is reported. To our knowledge, L. grimontii has never been reported as a cause of spontaneous bacterial peritonitis. The patient responded to antimicrobial therapy. Clinical and therapeutic implications are discussed.     

Oral findings in patients with obstructive sleep apnea syndrome.

OBJECTIVE: To evaluate the role of dental parameters that may contribute in increasing apneic activity in patients with obstructive sleep apnea syndrome (OSAS). METHOD AND MATERIALS: A total of 152 subjects (121 males and 31 females ) were examined from October 1999 until September 2001, for sleep disorder symptoms. All patients underwent polysomnography. Any abnormal or unusual features that could inhibit the upper airway of the oral cavity were evaluated by an oral pathologist. RESULTS: Statistical analysis of the independent structural variables and the respiratory disturbance index proved to be significant only in the cases of retropositioned or narrow hard palate with a vertically positioned soft palate, the type of breathing (oral breathing), and the enlarged uvula. CONCLUSION: The oral soft tissues seem to be more closely associated with OSAS. Therefore, the diagnosis of the structural features of the oral cavity by the clinician is useful to predict apneic activity.     

Changes in central serotonergic function as a correlate of duration of illness in paranoid schizophrenia

There is evidence that the duration of untreated psychosis may affect both the course and outcome of treatment in schizophrenic patients. In the present study, we used neuroendocrine probes to test the hypothesis that untreated psychosis may induce time-dependent changes in central serotonergic and dopaminergic neurotransmission. Prolactin responses to the administration of clomipramine (i.v.) and haloperidol (i.m.) were measured in healthy control subjects and in 16 never-treated male patients with DSM-IV diagnoses of schizophreniform or schizophrenic disorders of paranoid subtype, both before and after 5 weeks of treatment with haloperidol. In the drug-free state, schizophrenic patients exhibited significantly increased prolactin responses to clomipramine administration compared with both the healthy control subjects and the schizophreniform patients. Maximum prolactin responses to clomipramine in the total group of patients were positively correlated with the duration of psychotic illness and negatively correlated with changes in Positive and Negative Syndrome Scale (PANSS) total, negative symptoms and general psychopathology scores after 5 weeks of treatment with haloperidol. Prolactin responses to haloperidol challenge in the drug-free state were lower in the schizophreniform group than in the control and the schizophrenic groups, but the differences did not reach statistical significance. The results provide evidence that the persistence of psychotic psychopathology induces secondary neuroadaptive effects, which seem to involve changes in central serotonergic function.