[Initial clinical experience of left bundle branch pacing after transcatheter aortic valve implantation].

Objective: To investigate the efficacy and safety of left bundle branch pacing(LBBP) in patients after transcatheter aortic valve implantation (TAVI). Methods: This is a retrospective study. A total of 35 patients underwent TAVI and received pacemaker implantation from January 2018 to December 2020 in Beijing Fuwai Hospital were enrolled. Patients were divided into LBBP group (n=12) and right ventricular apex pacing (RVAP) group (n=23) according to the pacing position. The success rate of operation in LBBP group was calculated, and the occurrence of complications were observed, and the parameters of pacemaker were measured on the 3rd day and 1, 3 and 6 months after operation. The N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiographic and ECG indexes were compared between the two groups on the 3rd day and 1, 3, and 6 months after pacemaker implantation. Result: A total of 35 patients were included, The age was (76.4±7.7) years, including 19 males (54.3%). The procedure time ((86.58±17.10)min vs. (68.74±9.18)min, P<0.001) and fluoroscopy duration ((20.08±4.44)min vs. (17.00±2.26)min, P<0.001) were significantly longer in LBBP group compared with RVAP group. The operation success rate of LBBP group was 11/12. There was no serious operation related complications such as pneumothorax, hemothorax, electrode dislocation, infection, and lower limb bleeding. The patients were followed up for 7.43 (5.21, 9.84) months. The programmed parameters of pacemaker were in the ideal range and stable during follow-up. At 3 and 6 months after operation, the left ventricular ejection fraction in LBBP group was higher than that in RVAP Group (at 3 months: (60.75±2.89)% vs. (57.35±3.33)%, P=0.004; at 6 months: (63.17±3.33)% vs. (56.17±3.97)%, P<0.001), NT-proBNP values was lower in LBBP group than that in RVAP Group (at 3 months: 822 (607, 1 150)ng/L vs. 1 052 (902, 1 536)ng/L, P=0.006; at 6 months: 440 (330,679)ng/L vs. 783 (588, 1 023)ng/L, P=0.001). At 1, 3 and 6 months after operation, the QRS duration was shorter in LBBP group than that in RVAP group (1 month: 99 (97, 107)ms vs. 126(124, 130)ms, P<0.001; 3 months: 98(96, 105)ms vs. 129(128, 133)ms, P<0.001; 6 months: 96(94, 104)ms vs. 130(128, 132)ms, P<0.001). Conclusions: For patients with permanent pacemaker indications after TAVI, LBBP is feasible, safe and reliable. It could improve the cardiac function in the short term, the long-term effect of LBBP needs to be further observed.

[Endovascular recanalization of symptomatic non-acute intracranial arterial occlusion: a single center case series].

Objective: To investigate the feasibility and safety of endovascular recanalization for symptomatic non-acute intracranial arterial occlusion (NAICO). Methods: Twenty-five consecutive patients who underwent endovascular recanalization for NAICO between January 2017 and October 2019 at Department of Neurosurgery, Beijing Hospital were retrospectively reviewed.There were 20 males and 5 females, aged (60.5±11.0) years (range: 41 to 73 years).The preoperative modified Rankin score(M(Q(R))) was 2 (2.5)(range: 1 to 5).The occlusion time was 40 (54)days (range: 17 to 570 days).The demographic data were collected. The initial procedural results, including the rate of successful recanalization, periprocedural complications and data pertaining to angiographic and clinical follow-up were recorded. Results: Recanalization was successful in 20 of 27 occlusive lesions of 25 patients. Intraoperative complications occurred in 3 cases, including vascular perforation in 1 case, arterial dissection in 1 case, and perforator occlusion occurred in 1 case. The incidence of permanent complications was 3.7% (1/27). All 25 patients underwent clinical follow-up, with a median period of 8 months (range: 1 to 33 months), and 23 patients with improved or stable modified Rankin scale. One patient developed new ischemic symptoms 2 months after discharge, and 1 patient died of complications of bed rest.The results of the angiography follow-up (median 4 months, range: 2 days to 9 months) showed that reocclusion occurred in 5 of all 20 successfully recanalized patients. Conclusions: Endovascular recanalization for symptomatic NAICO is feasible, relatively safe, and efficacious in highly selected cases. However, further larger scale pilot studies are needed to determine the efficacy and long-term outcome associated with this treatment.

[Preliminary application of drug-coated balloon in patients with symptomatic intracranial vertebrobasilar artery stenosis].

Objective: To explore the safety and short-term efficacy of drug-coated balloon (DCB) angioplasty for patients with symptomatic intracranial vertebrobasilar artery stenosis. Methods: Sixteen patients with symptomatic intracranial vertebrobasilar artery stenosis who received DCB angioplasty from September 2018 to December 2019 at Department of Neurosurgery, Beijing Hospital were retrospectively reviewed. There were 15 males and 1 female, aged (63.1±9.2) years (range: 48 to 77 years). Patients' demographics, lesions characteristics, complications, clinical and imaging follow-up data were collected and analyzed. Results: A total of 19 symptomatic intracranial vertebrobasilar artery stenosis were successfully treated with DCB.The degree of stenosis of lesion was 75% (20%) (M(Q(R))) before operation and 0 (20%) after operation. One posterior circulation stroke due to perforator artery occlusion happened in peri-procedural period.With a mean imaging follow-up time of 5.5 months, there was no restenosis occurred. Within a mean clinical follow-up period of 6.3 months, no new symptoms happened. Conclusion: For patients with symptomatic intracranial vertebrobasilar artery stenosis, DCB angioplasty seems relatively high safety with satisfactory short-term clinical and imaging outcomes.

[Sole angioplasty with tiny balloon for high-risk complex symptomatic intracranial atherosclerotic stenosis].

Objective: To explore the safety and short-term efficacy of sole angioplasty with tiny balloon for symptomatic intracranial atherosclerotic stenosis (ICAS) patients with complex lesions refractory. Methods: Consecutive 11 patients with complex ICAS lesions treated by sole angioplasty with tiny balloon (diameter≤2 mm) from September 2016 to November 2017 at Department of Neurosurgery, Beijing Hospital were retrospectively reviewed. Patients' demographics, lesions characteristics, procedures, complications, and clinical and imaging follow-up data were collected. There were 6 male and 5 female patients with mean age of 63.6 years (range: 45 to 77 years). Clinical manifestations were transient ischemia attack (TIA) in 4 cases, progressive ischemic stroke in 3 cases, recurrent stroke in 3 cases, and 1 case for preparation of scheduled radical resection of colon cancer. ICAS locations were middle cerebral artery M1 segment in 5 cases, M2 segment in 1 case, anterior cerebral artery A1 segment in 2 cases, and intracranial vertebral artery in 3 cases. Mean degree of ICAS stenosis was 92%. Lesion morphology was type A in 3 cases, B in 4 cases and C in 4 cases by Mori classification. Forward flow by modified thrombolysis in cerebral infarction (mTICI) was grade 1 to 2a in 8 cases, 2b in 3 cases. Collateral compensation grading was grade 2 in 5 cases, grade 3 in 6 cases. Results: Technique success rate was 10/11, peri-procedural complication rate was 1/11. Post-procedural forward flow in all cases had been enhanced and 10 cases obtained mTICI 2b to 3. Ten patients got favorable outcomes (modified Rankin score 0 to 2) at discharge. With a mean clinical follow-up time of 5.4 months, 1 patient was found to have TIA recurrence. With a mean clinical follow-up time of 7.4 months, 1 patient was found to have TIA recurrence. Eight in 11 cases obtained imaging follow-up during 3 months, and none restenosis was found. Conclusion: For symptomatic ICAS complex lesions, sole angioplasty with tiny balloon demonstrates relatively high safety with satisfactory short-term clinical and imaging results.

Adaptive laser shock micro-forming for MEMS device applications.

Laser shock micro-forming is a non-thermal laser forming method that uses laser-induced shockwave to modify surface properties and to adjust shapes and geometry of work pieces. The magnitude and spatial distribution of the laser-induced shockwaves depend on the energy profiles of the laser beam focused on sample surfaces. In this paper, we present an adaptive optical technique to engineer spatial profiles of laser beams to control the shapes, sizes, and locations of the laser-induced shockwaves and the resulting forming features. Using a spatial light modulator, this adaptive laser beam forming tool was used to process free-standing MEMS structures in aluminum, which has led to highly uniform forming features. Shockwave simultaneously excited by multiple laser beams generated by the spatial light modulator and its effects on the micro-forming process were also studied. The results presented in this paper show that the adaptive optics laser beam forming is an effective and flexible method to generate shockwave with various shapes and sizes of wavefront and at multiple locations for laser processing at microscales.

[Study of correlation between carotid artery tortuosity and atherosclerotic carotid artery stenosis].

Objective: To investigate the correlation between carotid artery tortuosity and atherosclerotic carotid artery stenosis. Methods: A total of 73 patients who underwent carotid computed tomography angiography with unilateral atherosclerotic carotid artery stenosis at Department of Neurosurgery of Beijing Hospital from January 2011 to June 2016 were retrospectively reviewed. There were 51 males and 22 females ranging from 48 to 90 years old, the average age was (65.9±9.5) years. There were 38 patients with carotid stenosis in the left carotid artery and 35 in the right, the stenosis degree of carotid artery ranged from 30% to 90% with the median was 44.0% (25.5%). According to the degree of carotid artery stenosis, the patients were classified into mild stenosis group and moderate/severe stenosis group. There were 43 patients in the mild stenosis group with an average stenosis degree of (37.5±5.4)%, there were 30 patients in moderate/severe stenosis group with an average stenosis degree of (65.6±10.9)%. The carotid artery (CCA) tortuosity, extracranial internal carotid artery (EICA) tortuosity and CCA-ICA bifurcation tortuosity were quantified by measuring the CCA tortuosity index, EICA tortuosity index and the internal carotid artery (ICA) angle, respectively. Comparison of diseased and normal carotid arteries was performed using t test or Wilcoxon signed-ranked test. Results: There were no statistically significant differences in CCA tortuosity index (Z=-0.584, P=0.559), ICA angle (t=0.278, P=0.781), and EICA tortuosity index (Z=-0.377, P=0.706) between diseased and normal carotid arteries in 73 patients. The diseased carotid arteries showed larger ICA angles (39.0° (19.0°) vs. 30.0° (15.0°)) (Z=-2.439, P=0.015) in the mild stenosis group, but smaller ICA angles ((31.5±11.7)° vs. (39.1±16.2)°) (t=-2.529, P=0.017) in the moderate/severe stenosis group, compared with the contralateral normal carotid arteries. There was no statistically significant difference in CCA (Z=-0.720, P=0.472; Z=-0.013, P=0.990) and EICA tortuosity index (Z=-0.349, P=0.727; Z=-0.114, P=0.909) between diseased and normal carotid arteries. Conclusions: Compared with normal carotid arteries, carotid arteries with mild atherosclerotic stenosis demonstrate a more tortuous CCA-ICA bifurcation, while those with moderate/severe stenosis demonstrate a straighter CCA-ICA bifurcation. There is no correlation between CCA, EICA tortuosity and carotid artery stenosis.

[Association of serum albumin level and clinical outcomes among heart failure patients receiving cardiac resynchronization therapy].

Objective: To assess the relationship between serum albumin level and clinical outcome in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Methods: In this retrospective cohort study, 357 consecutive chronic heart failure patients receiving CRT between January 2010 and December 2015 were enrolled and divided into two groups based on pre-CRT serum albumin (albumin≥40 g/L, n=244; albumin<40 g/L, n=113). Clinical outcomes were defined as all-cause mortality (including heart transplantation) and rehospitalization due to worsening HF.Baseline characteristics were compared and all-cause mortality (including heart transplantation) and rehospitalization due to worsening heart failure (HF) were analyzed using Kaplan-Meier curves.Prognostic value of albumin level was evaluated in Cox proportional-hazards regression models. Results: Over a median follow-up time of 21 months, 45 patients (12.6%) died, 4 patients (1.1%) underwent heart transplantation and 100 patients (28.0%) were rehospitalized due to worsening HF. HF patients with pre-CRT albumin<40 g/L were related with worse NYHA function class, lower HDL-C level and ACEI/ARB use compared to HF patients with pre-CRT albumin≥40 g/L. Kaplan-Meier analyses evidenced lower survival rate in HF patients (log-rank test: P=0.000 4, χ(2)=12.60) and higher rehospitalization rate due to worsening HF (log-rank test: P=0.009, χ(2)=6.82) in HF patients with pre-CRT albumin<40 g/L.Multivariate Cox analyses indicated that serum pre-CRT albumin <40 g/L was an independent risk factor for all-cause mortality (HR=2.019, 95%CI 1.125-3.622, P=0.018) and HF rehospitalization (HR=1.517, 95%CI 1.014-2.270, P=0.043). Conclusion: Pre-CRT serum albumin level is associated with the severity of heart failure in CRT recipients.Patients with lower pre-CRT albumin level face increased risk of all-cause mortality and HF rehospitalization in chronic heart failure patients receiving cardiac resynchronization.

Evolutionary analysis of the ubiquitin gene of baculovirus and insect hosts.

Baculovirus is the only virus that has been found to encode the ubiquitin protein. In this study, ubiquitin sequences from 16 insects and 49 viruses were collected and compared. The resulting sequences were aligned with virus genomes. Then MAGE 5.0, k-estimated software, as well as other software programs were used for systemic evolutionary, selection pressure, and evolutionary distance analysis. The results of the pairwise ratio of non-synonymous to synonymous substitution values and evolutionary distances showed that ubiquitin from baculovirus and insect hosts have been under purifying selection during evolution and are thus evolutionarily conserved. Moreover, genes from insect hosts were more conserved than those in baculovirus. Analysis of the non-synonymous to synonymous substitution rates at each site and entropy calculations revealed the evolutionary status of every site in the ubiquitin genes of baculovirus and their hosts. Genome locations and phylogenetic trees indicated that granuloviruses and non-photosynthetic vegetation evolved, and granulovirus evolution was more similar to that of insect hosts. Our results suggest that the ubiquitin gene in baculovirus may have been acquired through horizontal transfer from the host.

Holographic fabrication of 3D photonic crystals through interference of multi-beams with 4 + 1, 5 + 1 and 6 + 1 configurations.

In this paper, we are able to fabricate 3D photonic crystals or quasi-crystals through single beam and single optical element based holographic lithography. The reflective optical elements are used to generate multiple side beams with s-polarization and one central beam with circular polarization which in turn are used for interference based holographic lithography without the need of any other bulk optics. These optical elements have been used to fabricate 3D photonic crystals with 4, 5 or 6-fold symmetry. A good agreement has been observed between fabricated holographic structures and simulated interference patterns.

Phylogenetic analyses of vector mosquito basic helix-loop-helix transcription factors.

Basic helix-loop-helix (bHLH) transcription factors play critical roles in the regulation of a wide range of developmental processes in higher organisms and have been identified in more than 20 organisms. Mosquitoes are important vectors of certain human diseases. In this study, Aedes aegypti, Anopheles gambiae str. PEST and Culex quinquefasciatus genomes were found to encode 55, 55 and 57 bHLH genes, respectively. Further phylogenetic analyses and OrthoDB and Kyoto encyclopedia of genes and genomes orthology database searches led us to define orthology for all the identified mosquito bHLHs successfully. This provides useful information with which to update annotations to 40 Ae. aegypti, 55 An. gambiae and 38 C. quinquefasciatus bHLH genes in VectorBase. The mosquito lineage has more bHLH genes in the Atonal, neurogenin (Ngn) and Hes-related with YRPW motif (Hey) families than do other insect species, suggesting that mosquitoes have evolved to be more sensitive to vibration, light and chemicals. Mosquito bHLH genes generally have higher evolutionary rates than other insect species. However, no pervasive positive selection occurred in the evolution of insect bHLH genes. Only episodic positive selection was found to affect evolution of bHLH genes in 11 families. Besides, coding regions of several Ae. aegypti bHLH motifs have unusually long introns in which multiple copies of transposable elements have been identified. These data provide a solid basis for further studies on structures and functions of bHLH proteins in the regulation of mosquito development and for prevention and control of mosquito-mediated human diseases.

Human SARS-CoV-2 has evolved to increase U content and reduce genome size.

Infections caused by SARS-CoV-2 have brought great harm to human health. After transmission for over two years, SARS-CoV-2 has diverged greatly and formed dozens of different lineages. Understanding the trend of its genome evolution could help foresee difficulties in controlling transmission of the virus. In this study, we conducted an extensive monthly survey and in-depth analysis on variations of nucleotide, amino acid and codon numbers in 311,260 virus samples collected till January 2022. The results demonstrate that the evolution of SARS-CoV-2 is toward increasing U-content and reducing genome-size. C, G and A to U mutations have all contributed to this U-content increase. Mutations of C, G and A at codon position 1, 2 or 3 have no significant difference in most SARS-CoV-2 lineages. Current viruses are more cryptic and more efficient in replication, and are thus less virulent yet more infectious. Delta and Omicron variants have high mutability over other lineages, bringing new threat to human health. This trend of genome evolution may provide a clue for tracing the origin of SARS-CoV-2, because ancestral viruses should have lower U-content and probably bigger genome-size.

All-fiber passively mode-locked thulium-doped fiber ring oscillator operated at solitary and noiselike modes.

This Letter presents an all-fiber mode-locked thulium-doped fiber ring oscillator based on nonlinear polarization evolution (NPE). Pumped by an erbium-doped fiber amplified spontaneous emission source, the construction of the laser cavity consisting of only fiber optic components can operate under two different regimes of solitary and noiselike (NL) pulses. Autocorrelation measurements are performed to extract features of these two regimes.

Ubiquitins of Bombyx mori nucleopolyhedrovirus and Helicoverpa armigera nucleopolyhedrovirus show distinct subcellular localization in infected cells.

Ubiquitin (UB) is a conserved protein that regulates a number of processes in eukaryotic cells. Nearly all lepidopteran baculoviruses encode UB homologs showing a partial sequence identity with human UB (Hu-UB). In this study, the sequence, predicted 3D-structure and subcellular localization of UB homologs encoded by two different nucleopolyhedroviruses of Bombyx mori (BmNPV) and Helicoverpa armigera (HaNPV) were compared. UBs of BmNPV and HaNPV (Bm-UB, Ha-UB, respectively) shared only 73% of sequence identity of the different aa in relation to Hu-UB being localized in non-conserved parts, namely in two heterogeneous regions of aa 15-32 and aa 53-60. Interestingly, Bm-UB and Ha-UB share the same seven lysines except for an additional Lys54 in Bm-UB. However, in spite of the sequence heterogeneity, Bm-UB and Ha-UB have a similar predicted 3D-structure. A difference in their subcellular localization during virus growth in insect cell lines was found in the late stage of formation of occlusion-derived virus (ODV). In particular Bm-UB was localized mainly and evenly in the nucleus, while Ha-UB on the nuclear membrane. These data suggest that (i) UBs, besides being engaged in various cellular processes, have a role in specific processes of virus growth, and (ii) Bm-UB and Ha-UB may show certain different activities associated with the virus growth.

Five beam holographic lithography for simultaneous fabrication of three dimensional photonic crystal templates and line defects using phase tunable diffractive optical element.

This paper demonstrates an approach for laser holographic patterning of three-dimensional photonic lattice structures using a single diffractive optical element. The diffractive optical element is fabricated by recording gratings in a photosensitive polymer using a two-beam interference method and has four diffraction gratings oriented with four-fold symmetry around a central opening. Four first-order diffracted beams from the gratings and one non-diffracted central beam overlap and form a three-dimensional interference pattern. The phase of one side beam is delayed by inserting a thin piece of microscope glass slide into the beam. By rotating the glass slide, thus tuning the phase of the side beam, the five beam interference pattern changes from face-center tetragonal symmetry into diamond-like lattice symmetry with an optimal bandgap. Three-dimensional photonic crystal templates are produced in a photoresist and show the phase tuning effect for bandgap optimization. Furthermore, by integrating an amplitude mask in the central opening, line defects are produced within the photonic crystal template. This paper presents the first experimental demonstration on the holographic fabrication approach of three-dimensional photonic crystal templates with functional defects by a single laser exposure using a single optical element.

Fabrication of two-layer integrated phase mask for single-beam and single-exposure fabrication of three-dimensional photonic crystal.

In this paper, we report a new design and fabrication of an integrated two-layer phase mask for five-beam holographic fabrication of three-dimensional photonic crystal templates. The phase mask consists of two layers of orthogonally oriented gratings produced in a polymer. The vertical spatial separation between two layers produces a phase shift among diffractive laser beams, which enables the holographic fabrication of inter-connected three-dimensional photonic structures. A three-dimensional photonic crystal template was fabricated using the two-layer phase mask and was consistent with simulations based on the five beam interference. The reported method simplifies the fabrication of photonic crystals and is amendable for massive production and chip-scale integration of three-dimensional photonic structures.

Woodpile-type photonic crystals with orthorhombic or tetragonal symmetry formed through phase mask techniques.

This paper simulates the photonic band structure in face-centered-orthorhombic and face-centered-tetragonal woodpile-type photonic crystals and shows the fabrication feasibility of these crystals with phase mask based holographic lithography. The experimental demonstration on SU-8 photoresist indicates that a single optical element can replace a complex optical setup for the holographic fabrication of woodpile-type photonic crystals. Photonic band gap calculation predicts the existence of full band gap in these crystals. Optimum band gap sizes are studied for crystals formed under various experimental conditions.

Activation of indices of cell-mediated immunity in bipolar mania.

BACKGROUND: Evidence supports that macrophages as well as lymphocytes and their products may be involved in the pathophysiology of psychiatric disorders. Whether patients with bipolar disorder have activation or reduction of immunity during a manic episode remains unclear. METHODS: The purpose of this case-control study was to investigate the lymphocyte proliferation to phytohemagglutinin (PHA), concanavalin A, and pokeweed mitogen, and plasma levels of soluble interleukin-2 receptor (sIL-2R) and sIL-6R in patients with bipolar mania (DSM-III-R). The subjects were 23 physically healthy patients with Young Mania Rating Scale (YMRS) scores > or = 26 as well as aged < or = 45 years and 23 age- and gender-matched normal control subjects. The above immune variables were measured in acute mania and consequent remission (YMRS scores < or = 12) among bipolar patients. RESULTS: The lymphocyte proliferation to PHA and the plasma sIL-2R levels, but not sIL-6R, of bipolar patients were significantly higher in acute mania than in consequent remission. These elevations were not due to differences in medication status. Only in acute mania were the plasma sIL-2R levels of patients significantly higher than control subjects. A positive correlation between the changes of manic severity and plasma sIL-2R levels was observed. Remitted bipolar patients and normal control subjects did not differ in any of these measures. CONCLUSIONS: Cell-mediated immunity activation in bipolar mania was demonstrated and may be through a specifically state-dependent immune response.

Fluvoxamine reduces the clozapine dosage needed in refractory schizophrenic patients.

BACKGROUND: Concomitant fluvoxamine use can potentially reduce the dosage of clozapine needed in treatment-refractory patients with schizophrenia. Previous reports have shown that fluvoxamine can increase plasma clozapine concentrations by inhibition of cytochrome P450 (CYP) 1A2. We evaluated the safety and efficacy of fluvoxamine, 50 mg/day, coadministration with clozapine, 100 mg/day, in refractory schizophrenic patients. METHOD: In this prospective study, 18 treatment-refractory patients with DSM-IV schizophrenia (10 nonsmokers and 8 smokers) were treated with clozapine at a target dose of 100 mg h.s. After steady-state conditions of clozapine had been reached, 50 mg/day of fluvoxamine was then added. Plasma levels of clozapine, norclozapine, and clozapine N-oxide were measured prior to fluvoxamine addition and on days 14 and 28 during combined treatment. Side effects and efficacy were monitored with standardized rating instruments. RESULTS: After 14 days of combined treatment, the mean +/- SD plasma clozapine level increased 2.3-fold to 432.4+/-190.9 ng/mL without further elevation on day 28. All patients completed the study without significant adverse side effects. Twelve of the 18 patients achieved plasma clozapine concentrations of at least 350 ng/mL. While plasma norclozapine levels also rose (but to a smaller extent), plasma clozapine N-oxide levels remained unchanged after the add-on therapy. Patients who smoked had 34% lower plasma clozapine concentrations than nonsmokers (NS). Three of the 4 patients who did not reach clozapine plasma levels of at least 300 ng/mL were smokers. Plasma norclozapine/clozapine ratios, especially in smokers, declined significantly with fluvoxamine addition. CONCLUSION: The addition of fluvoxamine, 50 mg/day, to low-dose clozapine, 100 mg/day, can raise plasma clozapine levels to at least 300 ng/mL in most patients. Only slight dosage adjustments with clozapine may be needed after fluvoxamine coadministration in some patients who smoke. Plasma clozapine levels remained stable after 14 days of fluvoxamine addition. The combined treatment was well tolerated, and clinical improvement was observed in our patients. Further long-term studies with this drug combination are needed to determine its economic impact.

Determination of calcium gluconate by selective oxidation with periodate.

A modified analytical method was developed which can accurately quantitate calcium gluconate and its pharmaceutical preparations in the presence of other calcium compounds or other cations able to complex with EDTA. The proposed method was based on the principle of the Malaprade reaction, according to which gluconic acid is selectively and quantitatively oxidized by sodium periodate. The content of calcium gluconate was calculated from the amount of gluconic acid found. The selective oxidation proceeded at 50 degrees C for 10 min, yielding approximately 100% recovery of calcium gluconate. The proposed method was accurate, precise, and superior to the compendia EDTA- complexometric method in terms of specificity.