Analysis of the Frequency and Onset Time of Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Induced by Antidepressants or Antipsychotics.

BACKGROUND: Hyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH) is a potentially fatal adverse effect of antidepressants (ADs) and antipsychotics (APs), although its frequency and onset time have not been well documented. OBJECTIVE: To analyze the frequency and onset time of AD- or AP-induced hyponatremia/SIADH. METHODS: We used plural data-mining techniques to search the US Food and Drug Administration Adverse Event Reporting System (FAERS) database for reports on hyponatremia/SIADH induced by psychotropic drugs from January 2004 to June 2020. For each item, we assessed the reporting odds ratio, 95% CI, median onset time, and Weibull distribution parameters. RESULTS: We identified 36 422 reports related to hyponatremia/SIADH. Signals were detected for all psychotropic drugs that we analyzed, except for clozapine. The median onset time of total AD-induced hyponatremia/SIADH was shorter than that of AP. For all ADs and APs except clozapine, hazards were considered to be the early failure type. In contrast, the hazard of clozapine was considered to be the random failure type. The limitations of this study included several reporting biases and the presence of confounding variables, particularly age. CONCLUSION AND RELEVANCE: Most ADs and APs were found to be associated with a risk for hyponatremia/SIADH. In addition, sufficient attention should be paid to signs of hyponatremia/SIADH in the early phase when most ADs and APs are administered. These data are potentially useful for determining AD- or AP-induced hyponatremia/SIADH in the early stage and for preventing its further aggravation into a serious condition.

Prevention and management of diarrhea associated with naldemedine among patients receiving opioids: a retrospective cohort study.

BACKGROUND: Naldemedine, a novel peripherally-acting mu-opioid receptor antagonist, has improved opioid-induced constipation in randomized controlled trials. The most frequent adverse event of naldemedine is diarrhea, which can cause abdominal pain and often leads to treatment discontinuation. We aimed to identify risk factors and appropriate management strategies for key adverse events including diarrhea associated with naldemedine, since those have not been extensively studied. METHODS: We conducted a multi-center retrospective cohort study. Eligible patients had cancer, had undergone palliative care at participating centers, had been prescribed regular opioids, and had taken at least one dose of naldemedine between June 2017 and March 2018. The primary endpoint was the incidence of diarrhea according to baseline characteristics. Secondary endpoints included the duration of naldemedine administration, daily defecation counts before and after starting naldemedine, duration and severity of diarrhea as an adverse event of naldemedine, other adverse events, and the incidence of constipation within 7 days after recovery from diarrhea. We defined patients who started naldemedine within three days of starting a regularly prescribed opioid as the early group, and the remainder as the late group. RESULTS: Among 103 patients who received naldemedine, 98 fulfilled the eligibility criteria. The median age was 68 years and 48% of the patients were female. Median performance status was 3, and the median oral intake was 50%. The median duration of naldemedine administration and overall survival were 25 and 64 days, respectively. The incidence of diarrhea in the early group (n = 26) was significantly lower than in the late group (n = 72) (3.9% vs. 22.2%, p = 0.02). Daily defecation counts increased after late (median 0.43 to 0.88, p < 0.001), but remained stable after early naldemedine administration (median 1.00 to 1.00, p = 0.34). Constipation after the diarrhea was resolved was common (53%), especially among patients who stopped naldemedine (78%). The diarrhea was improved within three days in 92% of patients who stopped other laxatives. CONCLUSIONS: The early administration of naldemedine is beneficial because it reduces adverse events including diarrhea. Diarrhea caused by naldemedine can be effectively managed by stopping other laxatives while continuing naldemedine.

[Optimum Volume of Water Needed for the Paste State of Pediatric Powders: Considerations Based on Yield Values and Applications to Generic Medicine].

To clarify the volume of water required to paste pediatric powders, we herein established a standard for the powder paste state by measuring yield values when water was added to powders. The powders used in the present study were selected from 8 types including original and generic drugs. Tipepidine hibenzate is prescribed in the pediatric field in combination with ambroxol hydrochloride and l-carbocysteine. The volumes of water needed to achieve the paste state of ambroxol hydrochloride between the original and generic drugs were similar. However, the volumes of water needed for l-carbocysteine markedly differed between the original and generic drugs due to differences in their additives. The spreadability of the mixture when water was added to the powders was evaluated using a spread meter. Among the powders tested in the present study, the yield value to achieve a paste state with the addition of water was approximately 1000 dyne/cm2. The optimum volume of water estimated from this yield value using the linear proportional relationship for the amount of powder may be applied to the mixture of each pediatric power for dosage/body weight.

Hematopoietic cell transplantation for myeloid/NK cell precursor acute leukemia in second remission.

Myeloid/natural killer cell precursor acute leukemia (MNKPL) is a rare leukemia subtype characterized by a high incidence of extramedullary infiltration. No appropriate treatment strategy has so far been developed. Acute myelogenous leukemia-type chemotherapy combined with L-Asparaginase is an effective treatment for MNKPL. Hematopoietic cell transplantation is a second option in refractory cases.

Effect of high fat diet on artificial oocyte activation following superovulation in mice.

The aim of the present study was to determine the effects of increased dietary intake and high fat diet (HFD) in mice on artificial oocyte activation by using puromycin or roscovitine. Six-week-old mice were fed as either a control diet group, an increased dietary intake group or an HFD group for 4 weeks. Oocytes were obtained following superovulation and were divided into three treatment groups (no activation treatment, calcium ionophore and puromycin treatment, and calcium ionophore and roscovitine treatment) and were incubated for 4 h. Retrieved oocytes and numbers of oocytes activated as assessed by morphological changes were compared among the three treatment groups. The proportion of degenerated oocytes in HFD mice was significantly higher than that in control diet mice. The rates of activation in oocytes treated with roscovitine were 90.3% in control diet mice, 89.8% in increased dietary intake mice and 67.9% in HFD mice. The rate of activation in oocytes treated with roscovitine in HFD mice was significantly lower than the rates in control diet mice and increased dietary intake mice. The rates of activation in oocytes treated with puromycin were 90.6% in control diet mice, 94.0% in increased dietary intake mice and 71.4% in HFD mice, and the rate of activation in oocytes treated with puromycin in HFD mice was significantly lower than the rates in control diet mice and increased dietary intake mice. HFD-induced obesity deteriorated induction of oocyte activation by roscovitine or puromycin in mice.

Involvement of propionate side chains of the heme in circular dichroism of myoglobin: experimental and theoretical analyses.

Incorporation of the heme into globin induces a prominent circular dichroism (CD) band in the Soret region. The appearance of heme optical activity is widely believed to arise from the interaction between the heme and aromatic residues of the globin. However, hemoglobin (Hb) containing the reversed heme exhibits a CD spectrum obviously different from that of native Hb, indicating that the interactions of heme side chains with globin contribute to the appearance of heme optical activity. We examined this possibility by comparing CD spectra of native myoglobin (Mb) and those of Mb reconstituted with synthetic hemes lacking vinyl and/or propionate. Replacement of 2,4-vinyl groups with methyl induced moderate changes. In contrast, replacement of 6,7-propionate groups with carboxylate resulted in complete disappearance of the positive Soret CD band. To get theoretical basis for the contributions of 6,7-side chains on the band, we investigated the CD spectra at a time-dependent density functional theory level. In the antiparallel conformation of the 6,7-side chains, the rotational strengths were calculated to be positive, on the other hand in the parallel conformation to be negative. We also found that the weak Soret CD band in 2,4-dimethyl-6,7-dicarboxyheme can be explained by canceling between different carboxyl conformers.

Highly enantioselective hydrogenative desymmetrization of bicyclic imides leading to multiply functionalized chiral cyclic compounds.

Highly enantioselective hydrogenative desymmetrization of bicyclic imides has been developed with chiral Cp*Ru(PN) catalysts. The present hydrogenation directly provides stereochemically well-defined cyclic compounds with excellent enantiomeric exessses, which might otherwise require a detour to reach.

Hydrogenation of N-acylcarbamates and N-acylsulfonamides catalyzed by a bifunctional [Cp*Ru(PN)] complex.

Awakening of the Cp one: The bifunctional complex 1 facilitates the interaction with substrates bearing less electrophilic carbon atoms than ketones, epoxides, and imides. The title reaction was applicable to the reduction of Evans' asymmetric alkylation products to the chiral alcohols along with good recovery of the chiral oxazolidinone auxiliary. EWG = electron-withdrawing group.

Transurethral ethanol injection therapy for prostatic hyperplasia: 3-year results.

PURPOSE: We assessed the medium-term (3-year) efficacy of transurethral ethanol injection therapy of the prostate (EIP) for benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 34 patients were followed for a median of 4.3 years after EIP. Mean age was 68.1 years and mean baseline prostate volume was 49.3 ml. With the patient under combined sacral and urethral anesthesia, dehydrated ethanol was injected into the prostate with endoscopic guidance. A urethral catheter was inserted postoperatively. RESULTS: Mean total ethanol dose was 6.4 ml and a catheter was required for a mean of 7.6 days postoperatively. Mean International Prostate Symptom Score was 21.8 points before EIP (in 34 patients), and decreased to 13.1 points after 3 years (in 17, p <0.01). Mean quality of life index decreased from 5.0 points before EIP to 2.8 points after 3 years (p <0.001). Mean peak urine flow rate was 8.3 ml per second before EIP and increased to 12.7 ml per second after 3 years (p <0.01). Mean residual urine volume decreased from 93 ml before EIP to 28 ml after 3 years (p <0.01). Mean prostate volume decreased from 49.3 ml before EIP to 45.7 ml after 1 year (p <0.001), but increased to 51.4 ml after 3 years. No major complications were experienced. By 3 years after surgery 59.0% of patients had not required further treatment. CONCLUSIONS: Transurethral EIP caused minimal complications while maintaining improvement of the prostate symptom score and an increased peak urine flow after 3 years.

Factors associated with failure of extracorporeal shock-wave lithotripsy for ureteral stones using Dornier lithotripter U/50.

BACKGROUND: In the present series of 170 patients who underwent extracorporeal shock-wave lithotripsy (SWL) treatment for ureteral stones, the authors determine which patients with ureteral stones had an unsuccessful outcome. METHODS: The records of 170 patients with ureteral stones who were treated with SWL using the Dornier lithotriptor U/50 (EMSE 140) between January 1998 and December 1999 were retrospectively investigated. One hundred and thirty-one patients were treated with SWL alone (single session, n = 98; multiple session, n = 33) and 39 patients required auxiliary treatment due to failure of SWL (33 with transurethral ureterolithotripsy (TUL), one with open lithotomy, and five with residual fragments who were followed up). These two groups were compared using multivariate logistic regression analysis. RESULTS: Lower ureteral stones and stones more than 12 mm in diameter were associated with a poor outcome of SWL. There were no significant differences in age, gender, number of stones, JJ stent placement, and degree of ureteral obstruction due to the stone between the two groups. The odds ratios of lower ureteral stones and stones > or = 12 mm were 4.18 and 2.57, respectively. CONCLUSION: Patients with distal ureteral stones and/or stones more than 12 mm in diameter were difficult to treat successfully with SWL. Alternatives such as TUL should possibly be considered as a first-line therapy for these stones.