Duloxetine-induced hyponatremia in an elderly patient treated with thiazide diuretics.

Hyponatremia is a known adverse effect of duloxetine, and it can lead to potentially life-threatening complications. Administration of thiazide diuretics also has been the cause of hyponatremia. We report a case of duloxetine-induced hyponatremia in an elderly patient treated with thiazide diuretics. An 86-year-old woman treated with the trichlormethiazide was admitted for vertebral compression fracture with disorientation and nausea on the 6(th) day of treatment with duloxetine. Laboratory findings revealed hyponatremia, hypo-osmolality, concentrated urine, and increased urine sodium. Syndrome of inappropriate antidiuretic hormone was considered, therefore, duloxetine, and trichlormethiazide was discontinued and treated with fluid restriction, furosemide and sodium chloride administered orally. Disorientation and nausea were improved after correction of hyponatremia. Health care practitioners should be aware of the possibility of duloxetine-induced hyponatremia, particularly in patients treated with thiazide diuretics.

Clinical experience with once-daily tacrolimus in de novo kidney transplant recipients from living donors in Japan: 1-year follow up.

INTRODUCTION: We assessed our clinical experience with de novo kidney transplant recipients from living donors who received once-daily tacrolimus (OD TAC). In addition, we investigated tacrolimus pharmacokinetics and compared the dose of tacrolimus in de novo kidney transplant patients treated with OD TAC or twice-daily tacrolimus (BD TAC). MATERIAL AND METHODS: Ten patients (3 ABO incompatible, 2 preemptive), who had received a living donor kidney transplant at our hospital since February, 2009, received OD TAC with mycophenolate mofetil, methylprednisolone, and basiliximab. OD TAC doses were adjusted to maintain tacrolimus trough levels in the range of 9-12 ng/mL. We assessed clinical and pharmacokinetic profiles. We compared average total daily dose of tacrolimus between the OD TAC and BD TAC groups. RESULTS: Patient survival and graft survival rates were 100% at 15.7 months. Acute rejection was not found clinically. The protocol biopsies (week 3 and month 3) did not reveal biopsy-proven acute rejection, either. No calcineurin inhibitor toxicity occurred. Doses in the OD TAC and BD TAC groups at week 3 posttransplant were 0.308 mg/kg/day and 0.149 mg/kg/day, respectively. CONCLUSIONS: OD TAC appears to have efficacy and safety equivalent to that of BD TAC. However, a larger dose of OD TAC compared to that of BD TAC may be required during the early period after kidney transplantation.

Difference in the emetic control among highly emetogenic chemotherapy regimens: Implementation for appropriate use of aprepitant.

Although antiemetic medication based on the emetogenicity of the cancer chemotherapy regimen is recommended, emetic control varies even among highly emetogenic chemotherapy (HEC). In the present study, we retrospectively investigated the rates of emetic control by a combination of granisetron, 5-HT3 antagonist and dexamethasone in various HEC regimens, including 5 single-day chemotherapy regimens such as gemcitabine/cisplatin (GEM/CDDP), epirubicin/cyclophosphamide (EPI/CPA), pemetrexed or vinorelbine/cisplatin (PEM or VNR/CDDP), doxorubicin/bleomycin/vinblastine/dacarbazine (ABVd) and rituximab/doxorubicin/cyclophosphamide/vincristine/prendisolone (R-CHOP21), and 2 multiple-day chemotherapy regimens such as 5-fluorouracil/cisplatin (5-FU/CDDP) and bleomycin/etoposide/cisplatin (BEP). Complete response (no emesis, no rescue treatment) during the overall period (days 1-5) was assessed as the primary endpoint. Chemotherapy-induced nausea and vomiting was well-controlled (complete response >70%) in GEM/CDDP and R-CHOP21, but not in other regimens. The effect of a triple antiemetic medication including aprepitant (APR) was subsequently examined in patients receiving EPI/CPA and 5-FU/CDDP. Complete response was significantly improved in patients receiving 5-FU/CDDP but not in those receiving EPI/CPA, although the complete protection from vomiting significantly increased in both cases. Of note, the administration of APR for 5 days, but not for 3 days, was required to completely block the incidence of vomiting during the 7 days of the observation period in patients receiving 5-FU/CDDP. These findings suggest that APR should be used appropriately based on the emetogenicity of HEC regimens.

Pharmacokinetic properties of a once-daily formulation of tacrolimus in patients with renal transplantation.

The present study was designed to determine the pharmacokinetic profiles of a once-daily formulation of tacrolimus (CAS 104987-11-3; TAC-once) in patients before and after introduction of renal transplantation. Pharmacokinetic parameters for tacrolimus were almost comparable among patients receiving TAConce before, 2 weeks after and 3 weeks after renal transplantation. Among various parameters, C(trough) correlated most closely with the area under the concentration-time curve during 24 h (AUCo-24) (R2 = 0.82, P < 0.001), while no consistent correlation was observed between AUCo_24 and concentrations at 2 h or 4 h, or the dose of TAC-once. The clinical outcomes such as the incidence of acute re-jection, renal tissue injury and cytomegalovirus infection were evaluated during the first 3 weeks and 3 months after transplantation, and the data were compared with the historical data obtained from patients who had received the conventional twice-daily formulation of tacrolimus (TAC-twice). There were no significant differences in the incidence of such clinical outcomes between the two groups. These findings suggest that C(trough) is useful for therapeutic monitoring of tacrolimus in patients receiving TAC-once. In addition, pharmacokinetics and clinical outcomes were comparable between TAC-once and TAC-twice formulations.

Usefulness of serum cystatin C to determine the dose of vancomycin in critically ill patients.

OBJECTIVES: Serum creatinine (Scr) is not a reliable marker of renal function in critically ill patients because of an enhancement of protein catabolism, which makes it difficult to adjust the dosage of renally eliminated drugs such as antibiotics. This study aimed to investigate whether serum cystatin C (Scys-C) could be used as a reliable marker of renal function. METHODS: We investigated whether Scys-C was a reliable marker of renal function in 56 critically ill patients. Subsequently, the usefulness of Scys-C to determine the initial loading and the maintenance dose of vancomycin was examined in 18 patients. Crea- tinine clearance (Ccr) was assessed from Scr and creatinine in urine collected over 24 h (24-h Ccr). KEY FINDINGS: There was a good correlation between 24-h Ccr and 1/Scys-C (r(2) = 0.616), whereas less marked correlation was observed between 24-h Ccr and 1/Scr (r(2) = 0.221). On the other hand, vancomycin concentration was predicted from population pharmacokinetic parameters based on a two-compartment linear model. There were significant correlations between real trough concentrations of vancomycin and the values predicted from Scys-C using various equations (r(2) = 0.416-0.488), while less pronounced relationships were observed between real concentrations and the values predicted from Scr (r(2) = 0.134-0.187). CONCLUSIONS: These findings suggest that Scys-C is a reliable marker reflecting renal function in critically ill patients and is applicable to determine the initial loading dose as well as the maintenance dose of vancomycin.

Significance of individual adjustment of initial loading dosage of teicoplanin based on population pharmacokinetics.

An initial loading dose of teicoplanin is required to reach the optimal trough concentration (> or = 10 microg/mL) rapidly. To attain the optimal teicoplanin concentration efficiently, an individual loading dose regimen based on population pharmacokinetics, in which the target trough concentration was set to 15 microg/mL, was defined. Among 70 patients, 33 patients received the individual loading dose regimen, 33 patients received the conventional loading dose regimen (200mg or 400mg every 12h on Day 1 followed by 200mg once daily) and 4 patients received no loading dose. The proportion of patients showing an optimal plasma concentration was 88% in the individual loading dose regimen but only 33% in the conventional loading dose regimen. No patient without a loading dose showed the optimal concentration. Both total loading dose and plasma concentration were significantly (P<0.001) higher in the individual loading dose group than in the conventional loading dose group. Notably, the trough concentration was almost constant in patients with individual loading doses ranging from 800 mg to 1800 mg. These findings suggest that individual adjustment of the initial loading dose of teicoplanin is potentially useful to attain the optimal concentration rapidly.

[Clinical analysis of hyposmia-associated taste dysfunction].

We clarified the clinical features of "flavor dysfunction," defined as olfactory dysfunction with self-reported hypogeusia but normal taste function in gustatory tests compared to those of "smell and taste dysfunction" hyposmia and hypogeusia in olfactory and gustatory tests. Patients with flavor dysfunction reported significantly milder taste loss than those with other smell and taste dysfunction. The major smell and taste loss etiology was upper respiratory tract infection (URI) in the flavor dysfunction group and the URI rate was significantly higher in the flavor dysfunction group than in the smell and taste dysfunction group. Smell identification thresholds in T & T olfactometry were not different between groups. Flavor dysfunction, hyposmia was treated medically but not with conventional hypogeusia medication. Medication including zinc was administered for other smell and taste dysfunction. Both groups significantly recovered from taste dysfunction. Our results indicate that treating olfactory dysfunction effectively improves flavor dysfunction but hypogeusia need not necessarily be treated. Hyposmia and hypogeusia must be treated together for other smell and taste dysfunction, making it vital that we conduct appropriate gustatory testing to correctly differentiate between flavor and other smell and taste dysfunctions.

Squamous cell carcinoma of the nasolacrimal duct.

Tumors originating from the nasolacrimal duct are exceedingly rare. Only a few cases have been reported previously. In advanced cases with extended tumor, differential diagnosis from lacrimal sac tumor is difficult. A 68-year-old Japanese man with intractable dacryocystitis was examined with intranasal endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). Squamous cell carcinoma extended from a medial site in the left orbit to the lacrimal orifice. En bloc resection was performed and histopathological examination of the surgical specimen using serial section suggested that the origin of the tumor was located in the nasolacrimal duct. This is the first case in nasolacrimal duct carcinoma whose differential diagnosis of origin has been studied in detail. We showed that pathological study using serial section along the duct provides useful information for diagnosing the tumor origin in addition to that obtained from imaging studies.

Influence of visual information and test paradigm on clinical olfactory test results.

OBJECTIVE: The goal of this study was to determine if visual information and test paradigms affect clinical olfactory test results. METHODS: Three hundred and ninety-seven Japanese patients with complaints of olfactory dysfunction were administered both a new clinical olfactory test, the Odor Stick Identification Test for Japanese (OSIT-J), and the Japanese benchmark olfactory test, T&T olfactometry. Four different methods were used to administer the OSIT-J combining paradigms using word or picture-word alternatives with the four-plus alternative method based on a top-down strategy or the two-step identification method based on a bottom-up strategy. OSIT-J scores were compared for the different methods, referring to benchmark scores obtained with T&T olfactometry. RESULTS: OSIT-J scores using picture-word alternatives and the four-plus alternative method showed a stronger correlation with T&T olfactometry test scores than those using word alternatives and the two-step identification method, respectively. The average OSIT-J scores of the four-plus alternative method using picture-word alternatives were significantly higher than those using word alternatives in anosmic and severely hyposmic patients. The time required to administer the OSIT-J using both picture-word alternatives and the four-plus alternative method was the shortest of the four OSIT-J methods. CONCLUSIONS: Visual information and test paradigms may affect clinical olfactory test results. The OSIT-J method using picture-word alternatives and the four-plus alternative method may be the most suitable for clinical practice.

[Safety and usefulness of the long-term intranasal topical treatment with steroids for olfactory dysfunction].

Intranasal topical steroids are commonly used for the treatment of olfactory dysfunction. Although the side effects are considered to be minimal, these have not been studied in detail. We examined the side effects of intranasal topical treatment with steroids in patients with olfactory dysfunction. We treated 62 patients with intranasal topical application of 0.1% betamethasone sodium phosphate (Rinderone) administered to the olfactory clefts. After treatment for 1 or 2 months, serum ACTH or cortisol was reduced in 42 (68% of total) patients, however, no clinical symptoms associated with steroid side effects were observed. The treatment was discontinued in 8 of these patients, who elected to withdraw from the treatment. In these patients, the serum ACTH or cortisol returned to normal a month after stopping the treatment. In the remaining 34 patients, the topical treatment was continued and in only 4 of these patients, minor steroid-associated side effects such as the sensation of facial swelling and facial hair thickening, appeared 2-5 months after beginning the treatment. These side effects disappeared within a month after stopping the treatment. Regarding the therapeutic efficacy, in 18 (78%) of the 23 patients who continued treatment for an average period of 5 months, steroid treatment significantly improved their olfactory dysfunction. In conclusion, although it is important to consider the potential side effects of long-term intranasal topical treatment with steroids for olfactory dysfunction, this treatment is a highly effective method against olfactory dysfunction with minimal side effects.

[A case report on congenital anosmia].

We report 2 cases of congenital anosmia, in a 13-year-old girl and the other in a 10-year-old boy. They reported having no concept of "smell". The girl has no complications but the boy has congenital microphthalmia and is completely blind. They showed scale-out results on both T & T olfactometry and intravenous Alinamin test. Brain MRI detected hypoplasia or lack of the olfactory bulbs, tracts, and olfactory sulci in the frontal lobe of the brain in both patients. Neither had endocrinal dysfunction. In the boy, we biopsied the nasal mucosa in the olfactory cleft and found it had no olfactory epithelial cells at all. We found MRI to be the most useful imaging for diagnosing congenital olfactory disturbance.