Search

Background and Aims Extended-release calcifediol (ERC), active vitamin D analogs (VDA), and nutritional vitamin D (NVD) are the predominant vitamin D therapies (VDTs) commonly used for treatment (Tx) of secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 non-dialysis chronic kidney disease (ND-CKD) and vitamin D insufficiency (VDI). Clinical trials have demonstrated varying efficacy on serum total 25-hydroxyvitamin D (25D) and intact parathyroid hormone (iPTH) across VDTs. This study aimed to descriptively assess the real-world experience of various VDTs in increasing 25D, reducing iPTH, and modifying serum calcium (Ca). Method Medical records of the first 376 adult patients with stage 3 or 4 CKD and a history of SHPT and VDI who met study criteria from 18 geographically representative United States nephrology clinics were reviewed from 1 year before through 1 year after initiation of VDT. Key study variables included patient demographics, medication usage, and laboratory results. The study population had a mean age of 69.5 years with gender and racial distributions representative of the US ND-CKD population. Patients were stratified into cohorts based on their index therapy at index date: ERC (n=174), VDA (n=55) and NVD (n=147). Results Patients treated with NVD were predominantly CKD Stage 3 (69.4%), while CKD Stage 4 were the majority of those treated with ERC (53.4%) and VDA (61.8%). The ERC Tx’ed subjects demonstrated an increase in 25D by 23.7 ± 1.6 ng/mL (p Conclusion Clinical effectiveness and safety varied across VDTs. ERC was the only VDT which significantly reduced mean iPTH in the real world setting despite highest mean levels at baseline among the three cohorts. Additionally, subjects treated with ERC demonstrated the largest mean increase in 25D and ERC was the only VDT which raised mean 25D to the normal range (>30 ng/mL). Patients treated with ERC and NVD saw no statistically significant impact on serum Ca and P levels; however, those treated with VDAs saw a small, but statistically significant increase in serum Ca levels.

Metoprolol tartrate (MT) as monotherapy was administered orally in 17 patients with mild hypertension. All other drugs were discontinued 2 weeks prior to MT therapy. The present study group consisted of 10 men and 7 women within the age range of 42 to 71 years (mean ± S.D. = 55.8 ± 8). MT was administered at an initial dose of 50 mg twice daily. Subsequently, the dose of MT was titrated on a biweekly basis for a period of 12 weeks until the diastolic blood pressure was < 90 mmHg or a maximum daily dose of 300 mg was administered. The blood-pressure-lowering effect of MT was found to be clinically satisfactory and statistically significant (P < 0.05). Mild fatigue and swelling of the extremities were seen in two patients each. Mild headache, transient diarrhea, and mild cloudiness of mind were seen in one patient. From this study it is concluded that MT is a safe and effective first-step antihypertensive agent. The long-term effect of MT as a monotherapy in the treatment of mild hypertension needs further clinical evaluation.

Discriminated escape behavior of mice in a T-maze was evaluated as a model for investigation of drug effects upon memory. All studies involved discriminated escape training trials on which footshock offset occurred following a correct goal-arm choice. Memory was assessed in retention tests that involved either reversal or relearning of the previously trained goal choice. Analyses of discriminated escape acquisition and training-retention interval were performed to identify parameters yielding either optimal or poor retention. Parameters yielding poor retention in untreated mice were used in studies involving drugs expected to improve retention. Pretraining treatment of mice with either physostigmine (0.08 mg/kg) or HydergineTM (0.64 mg/kg) yielded improved retention scores when training was minimal (a criterion of two consecutive correct choices) and the retention interval was long (168 hr). The effects of scopolamine (0.64 mg/kg) upon memory were assessed in the context of a short retention interval (24 hr) and more complete training (three consecutive correct choices), parameters yielding optimal retention in saline-treated mice. Scopolamine yielded poorer 24-hr retention performance when present during training, retention, or at both times. Overall, the results indicate that the discriminated escape procedures described are potentially useful for detection and analysis of pharmacologic modifications of memory processes.

Every day, thousands of people in the United States receive polycyclic antide pressants (PCAs) prescribed by their primary care physicians. We have exam ined the cardiovascular manifestations of polycyclic antidepressants in 14 patients with primary depression receiving various antidepressant drugs for a period of six months or more. None had suffered from any systemic illness. All 14 received a commonly prescribed PCA, such as doxepin, amitriptyline, imip ramine, desipramine or amoxapine, in therapeutic doses. None developed any significant adverse reaction. Left ventricular function, as determined by M-mode echocardiogram, was within normal limit in all pa tients. A twenty-four-hour ambulatory electrocardiogram revealed rare supraven tricular ectopic beats in 8 patients and ventricular ectopic activity (Lown grade 1) in 4 patients. In 1 patient, who received additional lithium carbonate for treatment of depression, both supraventricular and ventricular ectopic activity developed on rare occasions. In 4 of the 8 patients the plasma concentration of PCA was optimal or near optimal, and in 4 of the 8 patients it was subtherapeutic (even though these 4 patients had shown clinical improvement with continued polycyclic therapy). It appears from the present data that antidepressant therapy with PCAs pre scribed in therapeutic doses was well tolerated, without any significant adverse cardiovascular reaction, in otherwise healthy young patients with primary de pression.