Clozapine-induced elevated C-reactive protein and fever mimic infection

Clozapine-induced fever has been reported frequently, but clozapine-induced elevated serum C-reactive protein (S-CRP) over 100 mg/L with early onset, without associated myocarditis, has not been reported in the literature. In this case report, we present a case of an 80-year-old Slovenian female with dementia and psychotic symptoms who developed elevated S-CRP (122 mg/L) and fever (38.2°C) on the seventh day with 25 mg of clozapine daily, which improved after clozapine discontinuation. The patient did not have symptoms and signs of infection. This case report can be used to remind clinicians of keeping in mind the potential of clozapine associated with very high elevated S-CRP with fever, which can be easily confused with more serious conditions.     

HLA antigens and the antibody response after vaccination to hepatitis B

The aim of our work was the search for immunogenetic factors that influence the antibody response to HBs antigen. We analyzed the HLA-A, -B, and -DR antigen frequencies in 19 seropositive to HBs and 28 seronegative to HBs healthy persons finding an elevated frequency of B5 in the seropositive group (p value 0.037). After vaccination with Hevac B Pasteur vaccine of the seronegative persons, the low antibody response was associated with B13 (p value 0.041). An association between local side reactions to the vaccine and HLA A3 and B35 were also found (p values 0.042 and 0.022 respectively). The presented p values are not significant after correction for the number of antigens tested and for this reason our findings require confirmation in an independent study.     

Complex Osteochondral Lesions of the Talus Treated With a Novel Bi-Phasic Aragonite-based Implant

To present initial results of a novel, bi-phasic, porous, biodegrade, and cell-free aragonite-based scaffold for treating complex osteochondral lesions of the talus (OLT). Four subjects (2 males and 2 females; 34-61 years old) were operated on their ankles due to chronic and deep OLT-Hepple grades 4 or 5 (1.8-2.2 cm²). Three subjects had OLT on the medial central trochlea, and 1 had a combined medial and lateral lesions. OLT were exposed through medial malleolus osteotomy, with an additional lateral arthrotomy in the combined lesions. Bi-phasic porous osteochondral scaffolds (single implant or 2 implants) were implanted in a press-fit manner using a designated surgical toolset. Treatment outcome was followed clinically (Foot and Ankle Outcome Score, EQ-5D 3L, Tegner activity scale) and by medical imaging (radiographs, magnetic resonance imaging) from 18 to 32 months. All Foot and Ankle Outcome Score values increased from preoperative to final follow-up values (Symptoms 62 to 71, Pain 53 to 84, ADL 60 to 89, Sport 19 to 65, and QoL 18 to 47). EQ-5D 3L increased from 0.59 to 0.76, and Tegner activity values increased from 1.5 to 3. Kellgren-Lawrence ankle radiographic scores remained stable (2 to 2). Postoperative MR evaluation demonstrated cartilage defect fill of 75% to 100% respect to the native cartilage in 3 subjects (4 OLTs), while 1 lesion was filled 25% to 50%. No graft related serious adverse events or graft failures were reported. The use of a bi-phasic osteochondral biodegradable aragonite-based scaffold in the treatment of complex OLT during the reported period presented positive and promising clinical and radiologic outcome, without serious adverse events or graft failures.     

Dietary Intake and Status of Vitamin B12 in Slovenian Population

Vitamin B12 deficiency poses a health concern, especially in vulnerable populations. Dietary vitamin B12 intake was obtained by two 24 h dietary recalls and food propensity questionnaires in a representative Slovenian cross-sectional food consumption survey, SI.Menu (n = 1248 subjects; 10–74 years). For a subgroup of 280 participants, data on serum vitamin B12 were available through the Nutrihealth study. The estimated usual population-weighted mean daily vitamin B12 intakes were 6.2 µg (adults), 5.4 µg (adolescents), and 5.0 µg (elderly). Lower intakes were observed in females. Inadequate daily vitamin B12 intake (<4 µg) was detected in 37.3% of adolescents, 31.7% of adults, and 58.3% elderlies. The significant predictors for inadequate daily vitamin B12 intake were physical activity score in all age groups, sex in adolescents and adults, financial status and smoking in elderly, and employment in adults. Meat (products), followed by milk (products), made the highest vitamin B12 contribution in all age groups. In adolescents, another important vitamin B12 contributor was cereals. The mean population-weighted serum vitamin B12 levels were 322.1 pmol/L (adults) and 287.3 pmol/L (elderly). Low serum vitamin B12 concentration (<148 nmol/L) and high serum homocysteine (>15 µmol/L) were used as criteria for vitamin B12 deficiency. The highest deficiency prevalence was found in elderlies (7.0%), particularly in males (7.9%). Factors associated with high serum homocysteine were also investigated. In conclusion, although vitamin B12 status was generally not critical, additional attention should be focused particularly to the elderly.     

Additive Manufacturing of Honeycomb Lattice Structure—From Theoretical Models to Polymer and Metal Products

The study aims to compare mechanical properties of polymer and metal honeycomb lattice structures between a computational model and an experiment. Specimens with regular honeycomb lattice structures made of Stratasys Vero PureWhite polymer were produced using PolyJet technology while identical specimens from stainless steel 316L and titanium alloy Ti6Al4V were produced by laser powder bed fusion. These structures were tested in tension at quasi-static rates of strain, and their effective Young’s modulus was determined. Analytical models and finite element models were used to predict effective Young’s modulus of the honeycomb structure from the properties of bulk materials. It was shown, that the stiffness of metal honeycomb lattice structure produced by laser powder bed fusion could be predicted with high accuracy by the finite element model. Analytical models slightly overestimate global stiffness but may be used as the first approximation. However, in the case of polymer material, both analytical and FEM modeling significantly overestimate material stiffness. The results indicate that computer modeling could be used with high accuracy to predict the mechanical properties of lattice structures produced from metal powder by laser melting.     

Lithium and venlafaxine poisoning — a case report

In treatment of manic-depressive conditions long-term lithium therapy may be combined with an effective and relatively safe antidepressant venlafaxine. Combined overdose may increase the risk of early toxicity of both drugs and of delayed lithium intoxication, responding to symptomatic and renal replacement therapy. We present a patient with combined lithium and venlafaxine self-poisoning with nothing but delayed signs of lithium intoxication with the emphasis on early and late treatment. 41-year old woman attempted suicide by large amount of lithium and venlafaxine. On admission she was asymptomatic, but with increased serum lithium over 5mmol/L. After gastric lavage, active charcoal and laxative administration she was receiving IV fluids. After a delay of 63 hours she deteriorated acutely by disorientation, confusion, fasciculation and tremor and was readmitted to Intensive care unit. In spite serum lithium decreased to 2mmol/L clinical signs were attributed to delayed lithium intoxication. After symptomatic and renal replacement therapy the patient’s condition improved after few days. We conclude that decontamination procedures are effective in particular for venlafaxine poisoning. If increased serum lithium levels are noted renal replacement therapy may be started even in asymptomatic patients as delayed lithium intoxication is most likely after few days.     

Morphologic characteristics of central pulmonary thromboemboli predict haemodynamic response in massive pulmonary embolism

Objective On hospital admission, the morphology of the central pulmonary artery thromboemboli is an independent predictor of 30-day mortality in patients with massive pulmonary embolism (MPE). This may be due to the differential susceptibility of thromboemboli to thrombolysis. The aim of this study was to assess haemodynamic response to treatment in patients with MPE and morphologically different thromboemboli.Design Prospective observational study.Setting An 11-bed closed medical ICU at a 860-bed community general hospital.Patients Twelve consecutive patients with shock or hypotension due to MPE and central pulmonary thromboemboli detected by transesophageal echocardiography who were treated with thrombolysis between January 2000 through April 2002.Procedures Patients were divided into two groups according to the characteristics of detected central pulmonary thromboemboli: group 1, thrombi with one or more long, mobile parts; and group 2, immobile thrombi. Urokinase infusion was terminated when mixed venous oxygen saturation was stabilized above 60% for 15 min.Results At 2 h, the total pulmonary vascular resistance index was reduced more in group 1 than group 2 [from 27±12 mmHg/(l·min·m²) to 14±6 mmHg/(l·min·m²) (–52%) vs 27±8 mmHg/(l·min·m²) to 23±10 mmHg/(l·min·m²) (–15%), respectively, P=0.04]. In group 1 thrombolysis was terminated earlier than group 2 (89±40 min vs 210±62 min, respectively, P= 0.0024). The cumulative dose of urokinase used in group 1 was lower than group 2 (1.7±0.3 M i.u. vs 2.7±0.5 M i.u., respectively, P= 0.023).Conclusion Haemodynamic stabilization is achieved faster in patients with mobile central thromboemboli detected by transesophageal echocardiography during MPE.     

Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin

Sex hormone-binding globulin (SHBG) production in humans has been thought to be stimulated by estrogens and thyroid hormone and inhibited by androgens. However, recent data indicate that SHBG production in vitro is stimulated by both androgens and estrogens. This study was designed to determine what other hormonal factors regulate SHBG production. Since hyperinsulinemia and hyperprolactinemia both occur in disease states in which low serum SHBG levels are found, the effects of insulin and PRL were compared to and/or studied in combination with estradiol (E2), T4, and testosterone (T) in a human hepatoma cell line (Hep G2). Hep G2 cells were grown to near confluence in medium including 10% fetal calf serum, and then 72-h experimental incubations were carried out which used only fetal calf serum-free medium. Compared to control incubations, both insulin (10(-8) mol/L) and PRL (10(-8) mol/L) decreased SHBG production from 65.0 +/- 0.6 (+/- SE) to 46.8 +/- 1.1 and 46.8 +/- 1.2 nmol/10(6) cells, respectively (P less than 0.01). Insulin also inhibited both E2 and T4-stimulated SHBG production. T stimulated SHBG production to the same degree as E2. Finally, both E2 and insulin significantly increased cell number, an important consideration when expressing the effect of a hormone on SHBG production in cultured cells. We conclude that insulin and PRL inhibit SHBG production and confirm that T4, T, and E2 stimulate SHBG production in vitro. These findings suggest that insulin and PRL may be important factors in the regulation of SHBG production in vivo.