Minimum Serum Levels Research Articles

Objectives: Investigate whether there is any association between the levels of vitamin D in the blood and the seriousness of psoriasis or its development. Methods: The study is characterized as observational, retrospective, composed of 40 patients with psoriasis who had serum vitamin D levels, who underwent clinical care at a dermatology outpatient clinic in Passo Fundo/RS, from August 2019 to June 2021. Results: Of the 40 interviewees, 60% were female and 40% male. Phototypes II and III prevailed. Regarding family health history, 50% had a history of the disease. Regarding the duration of psoriasis, the predominant group was between 1-10 years (57.5%). The most prevalent psoriasis subtype was vulgaris (62.5%). Regarding serum vitamin D results, the lowest index was 15.2 ng ̸ mL, the highest was 42.3 ng ̸ mL and the average was 25.99 ng ̸mL. In the predominant age group, between 20-40 years, the proportion of patients with vitamin D was less than 30 ng ̸mL is 83.33%. The lower the phototype, the greater the proportion of patients with suboptimal serum vitamin D. In the group of patients with disease duration > 10 years, vitamin D levels were lower. There is no extreme difference in the effectiveness of treatments when analyzing the average, minimum and maximum serum levels of vitamin D. Conclusion: There was no relationship between serum levels of 25-hydroxyvitamin D (25OHD) and the development of psoriasis or even control – worsening of the clinical picture of disease.

AAV-monoclonal antibody expression protects mice from Ebola virus without impeding the endogenous antibody response to heterologous challenge

25-Hydroxyvitamin D [25(OH)D] has extra-skeletal effects, but it is not known whether the minimum sufficient serum levels for such targets, like muscle, differ from those for bone health (typically recommended at 20 or 30 ng/dL). Therefore, we derived and validated sex-specific thresholds for serum 25(OH)D predictive of poor physical function using 5 cohorts comprising 16,388 community-dwelling older adults (60.9% women). Using a cohort-stratified random two-thirds sample, we found incident slow gait was best discriminated by 25(OH)D<24.0 versus 25(OH)D>=24.0 ng/mL among women (Relative Risk=1.29; 95% CI 1.10-1.50) and 25(OH)D<21.0 versus 25(OH)D >=21.0 ng/mL among men (RR=1.43; 95% CI 1.01-2.02). Estimates from the remaining one-third validation sample were similar. Empirically identified and validated sex-specific 25(OH)D thresholds from multiple well-characterized cohorts of older adults may yield more biologically meaningful definitions in important sub-populations. Such thresholds may serve as candidate reference concentrations or inform design of vitamin D intervention trials in older adults.

Appropriate medication of intensive care patients is complicated by disturbed organ functions and organ failure, pathophysiological changes in severely ill patients as well as possible sepsis, ongoing haemodialysis for renal and hepatic insufficiency, varying pharmacokinetics/-dynamics (PK/PD) of drugs as well as numerous drug interactions. Illustration of an interdisciplinary approach in daily clinical practice to optimise regular "polymedication" as well as the ongoing medication of patients prior to surgical interventions as indicated and as part of the appropriate peri- and postoperative intensive care management. A so-called "drug interaction stewardship" (DIS) is very similar to the already established "antibiotic stewardship" (ABS) during daily clinical routine of an intensive care unit and has been implemented. In addition, therapeutic drug monitoring (TDM) has been extended to antibiotics/antimycotics (such as meropenem, piperacillin-tazobactam, ceftazidime, linezolide, voriconazole, fluconazole, caspofungin), for which TDM had not yet been established. This was in a consecutive cohort of patients with abdominal surgery over a defined time period and was part of a systematic clinical single centre observational study (tertiary centre). From 01 - 2012 to 08 - 2016, 1,454 single drug patient consultations led to 385 (26.5%) changes in medical treatment, which had been previously initiated by an experienced intensive care physician. Most frequently in 156 cases (10.7%) this was due to newly calculated PK/PD. Analysis of 2,333 TDM samples resulted in a minimum serum level within the adequate range in 1,130 cases (48.4%). In 427 cases (18.3%), the drug serum level was too low and in 776 subjects (33.3%), prompting a change in the type, dose, dose interval and application route. DIS and TDM provide a high rate of detection of unwanted drug interactions and inappropriate drug levels in surgical intensive care patients and help to assure targeted therapy changes.

Minimum serum level of 25-hydroxyvitamin D based on classical vitamin D effects, in our hospital's healthcare area

To investigate the plasma concentrations of cytokines and vasoactive molecules in patients with coronary heart disease (CHD) in the presence of hypertension in relation to the angiotensin-converting-enzyme (ACE) inhibitor level reflecting the degree of renin-angiotensin-aldosterone system (RAAS) inhibition. 72 patients with NYHA functional class (FC) II-III angina pectoris and 40 healthy persons at the age of 47-65 years were examined in a controlled cohort study. Enzyme immunoassay was employed to determine the serum concentrations of interleukins (IL) (IL-2, IL-12, IL-17A, and IL-24), the vasoactive molecules of bradykinin, serotonin, ACE, angiotensin-II (AT-II), NO, and endothelin-1 (ET-1), and plasma renin activity. In addition, the plasma level of the tetrapeptide N-acetyl-Ser-Asp-Lys-Pro was used as a marker for ACE inhibition. The patients with CHD occurring in the presence of hypertension compared with the apparently healthy individuals displayed decreased ET-1 and NO production along with elevated levels of serotonin, AT-II, as well as IL-17A and IL-12. The found changes were accompanied by reduced renin activity. Thus, the individuals with low ACE inhibitor levels showed more pronounced production of the proinflammatory cytokine IL-17A, as well as high plasma concentrations of ACE and NO. The high ACE inhibitor level that reflects patient adherence to appropriate antihypertensive therapy is associated with the reduced production of IL-2 and with the minimum serum levels of ACE, AT-II, and NO, being characterized by the high production of IL-12 and serotonin at the same time. In patients with CHD and hypertension, the high plasma enzyme inhibitor concentration that reflects the activity of appropriate antihypertensive therapy, by contributing to the strengthening of the mechanisms of relaxation of blood vessels, is associated with the risk for proinflammatory activation of whole blood cells and platelets. The mean ACE inhibitor levels that reflect moderate RAAS suppression and are characterized by a relatively low proinflammatory activation of mononuclear cells may be more preferable than the maximum ones, from the point of view of slowing the progression of the subclinical inflammatory process of the vascular wall and preventing possible CHD exacerbations. This determines the feasibility of estimating the plasma level of an ACE inhibitor to control the depth of inhibition of RAAS activity.

Background: Bacterial sepsis is highly prevalent among premature infants. Amikacin is an antibiotic widely recommended for the treatment of neonatal sepsis, one of the consequences of which might be nephrotoxicity. The present study aimed to compare the efficacy and nephrotoxicity of multiple daily dosing (MDD) and once-daily dosing (ODD) of amikacin in preterm infants suspected of sepsis. Methods: This triple-blind, randomized, controlled clinical trial was conducted on 40 premature infants suspected of sepsis, who were randomly divided into two groups. In addition to ampicillin, one group was administered with the standard daily dose, and the other group received an ODD of intravenous amikacin. Maximum and minimum serum levels of amikacin and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured in both groups. Data were extracted and analyzed based on the research hypothesis and literature review. Results: No significant differences were observed between the study groups in terms of gender, gestational age, mode of delivery, birth weight, and Apgar score. After the intervention, mean plasma creatinine reduced in both groups, while the mean reduction was significantly higher in the group administered with the ODD of amikacin (P=0.0001). However, mean changes in the urine NGAL had no significant difference between the groups (P=0.635). Minimum and maximum serum levels of amikacin in the study groups indicated a more significant reduction in mean level of the infants administered with the ODD of amikacin compared to the MDD group (P=0.0001). Conclusion: Considering the higher maximum and lower minimum levels of amikacin in the neonates receiving the daily dosage regimen, it seems that this regimen is more effective in the treatment of sepsis in preterm infants. Moreover, no significant difference was observed in the efficacy and nephrotoxicity of the daily amikacin dosing in the premature infants suspected of sepsis compared to those treated by multiple doses of amikacin.

Liver transplantation (LT) in patients with hepatitis B virus (HBV) infection is associated with a high rate of graft loss and poor survival, unless re-infection can be prevented. Human hepatitis B immune globulin (HBIG) has long been utilized to prevent re-infection. More recently, an anti-viral agent has been utilized along with HBIG. However, the regimens utilized have varied considerably among LT programmes and the optimal regimen has never been defined. We conducted a retrospective analysis of 41 patients who underwent LT for HBV at our centre since 1985 and received either HBIG with or without an anti-viral agent. The mean age of these patients was 46 years; 81% were male and 88% white. The mean and maximal follow-up were 5.9 and 15 years respectively. Eight out of 15 E-antigen-positive patients who received HBIG alone developed recurrence after a mean of 17 months. In contrast, none of 10 E-Ag-negative patients who received HBIG alone and none of the 10 E-antigen-positive patients who received both HBIG and either lamivudine or adefovir developed recurrence. As long as the anti-HB surface remained detectable, no absolute minimum serum level appeared to lead to recurrent HBV. We concluded that recurrence of HBV following LT can be prevented in E-antigen-positive patients with a combination of HBIG and an anti-viral agent. In contrast, recurrence can be prevented in E-antigen-negative patients with HBIG alone. Maintaining a serum anti-HB surface level above a minimum arbitrary titre of 200 pg/mL did not appear to be necessary for effective HBIG prophylaxis.

Insulin resistance (IR) can be induced by high amounts of growth hormone (GH). To set up, in acromegaly without diabetes mellitus, a correlation between the disease activity in GH-secreting adenoma (AA) - assessed by minimum GH serum level during an oral glucose tolerance test (OGTT) - and severity of insulin resistance (IR), assessed by HOMA-IR index. 75 out of 88 consecutive patients with acromegaly hospitalized in our department were included in this study. 13 patients proved to have diabetes mellitus and were excluded. Serum glucose, GH and insulin levels were measured by immunoradiometricassay basal and at 30, 60 and 120 minutes after a 75 g OGTT in 88 patients with active or cured acromegaly. IR was assessed using HOMA-IR index (Homa-IR=basal serum glucose (mg/dl) x basal serum insulin (mU/L)/22.5 x 18). A value over 2.5 was considered indicating IR. Out of 75 patients without diabetes mellitus, 36 subjects (48%) were presenting with IR (34 with active disease, 2 cured). We found a significant positive correlation (r=0.56, p<0.001) between AA and HOMA-IR. The GH minimal level corresponding to the intersection of the exponential regression curve with the HOMA-IR level of 2.5 was 8.8 ng/mL, a cut-off point indicating IR with 82% specificity and 78% sensitivity. The odds ratio for developing IR becomes significant at a minimum GH level during OGTT of 2 ng/mL (odds ratio 7.6, 95% confidence interval 2-29). The severity of IR revealed by acromegaly correlates with GH production. A GH serum level higher than 2 ng/mL during OGTT indicates an increased risk for developing IR. This cut-off level of GH can be used as one of criteria of cured disease, regarding the lack of metabolic effects.

Valproic Acid as Adjunct to Induction Therapy in Patients with Acute Myeloid Leukemia: First Results of Two Randomized Studies of the AMLSG.

G-CSF given as split dose increased the harvested number of CD34+ cells in comparison to a once daily schedule, but the mechanism is poorly understood. To investigate the schedule dependency of G-CSF in healthy volunteers with respect to CD34+ cell mobilization, the same dose of G-CSF was applied in four healthy volunteers in two different schedules (once daily vs. split doses twice daily) in a crossover design after a washout period of 3 months. CD34+ cell kinetics in serum were determined as well as G-CSF serum kinetics on Days 1 and 4 after stimulation. In all volunteers, the twice daily schedule led to a higher CD34+ cell count after 4 days of G-CSF stimulation (median, 94.5 vs. 47/ microL; p = 0.05). On Days 1 and 4, there was a higher peak serum concentration of G-CSF serum level after the once daily application (15,175 vs. 6,859 pg/mL and 7440 vs. 2388 pg/mL, respectively) than after the twice daily schedule. In contrast, after the once daily application the minimum serum level of G-CSF serum level was lower than after the twice daily schedule (663 vs. 1361 pg/mL and 246 vs. 441 pg/mL, respectively). No difference of area under the curve for G-CSF was observed on Days 1 and 4 after G-CSF stimulation. It is suggested that application of G-CSF twice daily leads to a higher CD34+ cell mobilization owing to a higher minimum serum level and therefore to a more continuous serum baseline level resulting in a more efficient CD34+ cell mobilization.

The purpose of this study was to determine if there are any correlations between carbamazepine serum levels of epileptic mothers during pregnancy and the brainstem auditory evoked potentials in their infants as an index of drug neurotoxicity in newborns exposed prenatally. We included 20 epileptic mothers with carbamazepine medication and their 20 otherwise healthy infants. The study was conducted from September 1, 1993, to December 15, 1999. Serum carbamazepine determinations were performed monthly by enzymatic immunoanalysis in the mothers, and the averages for each trimester during pregnancy were calculated. Brainstem auditory evoked potentials were performed at 10.2 +/- 4.6 weeks of postnatal life. Pearson's correlations were calculated between carbamazepine serum levels during pregnancy and waves and interwave intervals of brainstem auditory evoked potentials. Both examinations were performed without knowledge of the results of the other investigations. No alterations in the infants' brainstem auditory evoked potentials were evident, and carbamazepine determinations were within therapeutic levels. Significant Pearson's correlations between latencies of waves III and V and third trimester of carbamazepine serum concentration levels and I-V interwave intervals to third-trimester minimum serum levels of carbamazepine were found. The findings suggest that the higher carbamazepine levels in mothers are related to increased latencies in waves III and V and I-V interwave intervals in infants subclinically, which could be an early index of fetal neurotoxicity.

Factors such as age, the dose of nifedipine administered in the diet, serum drug level, duration of drug administration, and sex which may influence nifedipine-induced gingival overgrowth were examined in a rat model using 20-, 50-, and 90-days-old male and female rats. Oral administration of nifedipine (50 to 250 mg/kg diet) increased the serum level of the drug in a dose-dependent manner in both males and females. However, a higher serum level was required in females than males to attain the same degree of gingival overgrowth. The minimum dietary concentrations of the drug required to elicit gingival overgrowth in males and females were 150 and 100 mg/kg, respectively, which gave respective minimum serum levels of 800 and 1100 ng/ml. The degree of overgrowth depended on the serum concentration of the drug after it had reached the required minimum in male and female animals. Administration of nifedipine (250 mg/kg diet) for 20 days was enough to induce maximal overgrowth, but this induction occurred only in rats that started to receive the drug when they were 20 days old, not in those that started at 50 and 90 days of age for the same administration period of 55 days, and the overgrowth regressed and the gingiva were normal 40 days after ceasing drug administration. These results suggest that gingival overgrowth occurred in accordance with the drug concentration in the diet, as well as that in the serum, and was more likely to occur in males and younger individuals.

Postantibiotic effect of roxithromycin on streptolysin O production, hydrophobicity, and bactericidal activity of PMNL by Streptococcus pyogenes.

Determination of glibenclamide and its two major metabolites in human serum and urine by column liquid chromatography

Twenty‐two consecutive patients with rickets were studied in Benghazi, Libya. All were less than 2 years old. Rickets was associated with traditional cultural habits that limited sunshine exposure of the mothers and their infants, and with breast‐feeding. Serum concentrations of the vitamin D metabolites 25‐hydroxyvitamin D (25‐OHD), 1,25‐dihydroxyvitamin D, and 24,25‐dihydroxyvitamin D, and other parameters of mineral metabolism were typical of vitamin D deficiency disease, as was the biochemical and clinical response to treatment. Minimum safe serum levels of 25‐OHD (20 nmol/L), and the serum levels of vitamin D metabolites in response to vitamin D treatment, were identical to previously obtained results from native Norwegian and Norwegian immigrant children with rickets, suggesting lack of racial differences in response to vitamin D. Fifty percent of the patients had adequate levels of vitamin D metabolites at the time of diagnosis, indicating that they had recently received oral vitamin D or cutaneous exposure to sunshine. Many cases of rickets in the area may, therefore, be spontaneously cured when the children's maturity allows adequate mobility and independence to achieve exposure to sunshine.

To investigate the feasibility of administering perphenazine decanoate (PD) at double the depot injection interval compared with perphenazine enanthate (PE), 32 patients with chronic psychosis on a stable PE maintenance treatment entered the study. The antipsychotic effect was assessed by the Brief Psychiatric Rating Scale (BPRS) and adverse symptoms by using the Simpson & Angus rating scale. In addition, especially constructed scales for sedation and akathisia were used. Minimum and maximum serum levels of perphenazine were measured throughout the study. The results of this study indicate that it is feasible to substitute PD for PE provided that the patient is on a stable maintenance treatment with PE. No changes of clinical chemistry or body weight related to drug treatment were observed. No severe adverse symtoms were encountered, and in general both depot preparations were well tolerated. However, perphenazine decanoate (PD) seems to offer distinct advantages over perphenazine enanthate (PE) as depot ...

Serum neuroleptic activities required to inhibit relapse in schizophrenic patients — A study by radioreceptor assay

The efficient in vitro inhibition of hepatitis B virus DNA polymerase by trisodium phosphonoformate (PFA, INN: foscarnet sodium) and its low toxicity suggested that PFA could be used as a therapeutic agent for hepatitis B infection. PFA was also found to inhibit woodchuck hepatitis virus (WHV) DNA polymerase in vitro. As a model to test PFA's eventual effect, chronically WHV infected woodchucks were treated with PFA. The animals were treated twice daily in a dosage which gave a minimum serum level of PFA corresponding to an in vitro inhibiting effect on WHV DNA polymerase of about 40%. The concentration in liver tissue was found to be 15% below serum level. The amount of WHV particles in serum was followed by DNA polymerase assay. No effect on WHV production could be seen during 2 weeks' treatment. No change of the in vitro sensitivity to PFA of the WHV DNA polymerase was seen. These results indicate that the WHV associated DNA polymerase has no role in the production of viral particles.

A mathematical model and resulting computer program for simulating blood-level versus time profiles of drugs exhibiting saturable elimination processes are described and evaluated. The iterative digital-analog simulator (IDAS) program consists of two sections--a simulation (SIM) module and an iteration control (IC) module. The SIM module predicts minimum and maximum serum drug levels based on a dose and a dosing interval. The IC module takes the minimum and maximum serum levels from the SIM module and produces a new dose (for a new maximum serum level) and a new dosing interval (for a new minimum serum level). The new dosing information is fed back into the SIM module and the iteration process is repeated until the predicted minimum and maximum levels converge on desired levels set by the user of the program. The model and program were tested by comparing simulation results with actual patient data for phenytoin (seven patients) and theophylline (three patients). The ability of the program to converge on correct doses and dosing intervals was evaluated under a variety of given conditions. The mean difference between actual and simulated profiles was 0.286 mg/liter and 1.5 mg/liter for phenytoin and theophylline, respectively. IDAS produced dose and dosing interval estimates within desired precision given a variety of initial input data. The results encourage prospective clinical investigation of the reliability and validity of the method.