Prediction of Nursing Home Admission Using the FRAIL-NH Scale Among Older Adults in Post-Acute Care Settings.

OBJECTIVES: The FRAIL-NH scale was developed to identify frailty status in nursing home residents. The purpose of this study was to examine the utility of the FRAIL-NH scale for predicting nursing home admission among patients in post-acute care settings. Design/ Setting/ Participants: This single-center, prospective, observational cohort study included participants aged 65 years or older who were admitted to a community-based integrated care ward (CICW) between July 2015 and November 2020. MEASUREMENTS: Using the CICW database, we retrospectively classified participants as robust, prefrail, or frail based on the FRAIL-NH scale the score by identifying variables from our database that were most representative of each component. The following data were collected: examination findings, CICW admission and discharge information, length of CICW stay, and nursing home admission. The participants were divided into two groups based on whether or not they were admitted to a nursing home after CICW discharge. The hazard ratios (HRs) and 95% confidence intervals (CIs) for nursing home admission were calculated according to the FRAIL-NH categories using the Cox proportional hazards models with reference to the robust group. In the multivariate adjusted model, we adjusted for age, sex, nutritional status, cognitive function, living status, and economic status. RESULTS: Data of 550 older adults were analyzed, of which 118 were admitted and 432 were not admitted to a nursing home. The frail group had a higher risk of nursing home admission (HR, 2.22; 95% CI 1.32-3.76) than the robust group. CONCLUSIONS: This study showed that the FRAIL-NH scale was beneficial for predicting nursing home admission among older adults in the post-acute care setting. Thus, assessment using the FRAIL-NH scale may help to consider preparation and support for life after discharge.

Prenatal sonographic diagnosis of Beckwith-Wiedemann syndrome in association with a single umbilical artery.

Beckwith-Wiedemann syndrome is an inherited disorder most commonly characterized by prenatal or postnatal overgrowth, macroglossia, omphalocele, unusual earlobe creases, and increased risk of neoplasia. Several reported cases of this syndrome have been prenatally diagnosed, but no report has described the occurrence of this syndrome in association with a single umbilical artery. We report a case in which prenatal sonographic examination demonstrated fetal overgrowth, macroglossia, and omphalocele together with a single umbilical artery; our prenatal diagnosis of Beckwith-Wiedemann syndrome was confirmed after birth of the infant. The possibility of this syndrome should be considered when performing a detailed sonographic examination of a fetus with a single umbilical artery.

Successful treatment of primary fetal hydrothorax with hydrops by pleuroamniotic shunt placement.

We treated a case of primary fetal hydrothorax with hydrops. A pleuroamniotic shunt catheter inserted at 30 weeks accomplished resolution of hydrops and was maintained until cesarean delivery at 34 weeks with no need for further prenatal intervention. At age 9 months, the infant showed no effusion or pulmonary compromise.

Autosomal recessive hydrocephalus due to congenital stenosis of the aqueduct of sylvius.

Isolated hydrocephalus due to congenital stenosis of the aqueduct of Sylvius is almost always an X-linked recessive inherited condition. We describe a brother and sister with isolated hydrocephalus from congenital aqueductal stenosis. We believe that these two occurrences represent a rare autosomal recessive form of this abnormality. In assessing a first known occurrence of hydrocephalus with stenosis of the aqueduct of Sylvius in a family, the rare possibility of autosomal inheritance must be considered in genetic counselling.

Transplacental exposure to antipsychotic drugs during pregnancy and megacystis in the fetus.

Urinary retention is an adverse effect of antipsychotic drugs that has not been previously reported in the fetus. We have diagnosed megacystis in a fetus possibly caused by transplacental exposure to the antipsychotic drugs being administered to the mother. Two weeks after the mother stopped taking the drugs, the size of the enlarged fetal urinary bladder returned to normal. Sonographic examination of the neonate revealed an anatomically normal urinary tract, with a normal bladder capacity and urination.

[Three cases of carotid cavernous sinus fistulas where the main ocular manifestation was restricted ocular motility].

BACKGROUND: Some cases of carotid cavernous sinus fistulas (CCFs) have few ocular congestive signs and symptoms. These cases need to be accurately diagnosed as having CCFs. CASES: Three patients with CCFs without ocular congestive signs or symptoms developed unilateral abducens restriction and visited our clinic. FINDINGS: Color Doppler imaging revealed retrograde flow of the superior ophthalmic veins bilaterally in the three cases. The diagnose of CCF was confirmed by cerebral angiography. CONCLUSION: It is sometimes difficult to diagnose CCF, when a patient without ocular congestive signs or symptoms shows disturbed ocular motility as the only ocular manifestation. In such cases, color Doppler imaging may show the presence of CCF.

Brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP) levels in normal pregnancy and preeclampsia.

OBJECTIVE: Our purpose was to evaluate plasma levels of brain natriuretic peptide (pBNP) and cyclic guanosine monophosphate (pcGMP) in preeclamptic patients and controls. STUDY DESIGN: Blood samples were obtained from 35 patients with preeclampsia and from the same women during the subsequent puerperal period. The control group consisted of normotensive pregnant women, matched with the patients for age, gestational age, and parity. The concentrations of pBNP and pcGMP were determined by the RIA method. Statistical analysis was performed using the Mann-Whitney's U test. RESULTS: The pBNP level in the preeclampsia group was significantly increased, to 7-fold that of the control group. The pcGMP level was 50% higher in the preeclampsia group than in the control group, but this was not significant. Both the pBNP level and the pcGMP level in the puerperal period did not significantly differ between the patients and the controls. CONCLUSION: The pBNP concentrations increased in the preeclamptic women, and then these compensations were normalized in the puerperal period.

Temporal alterations of endothelial-vasodilator functions in lung injury induced by monocrotaline.

To assess the time course of alterations in pulmonary endothelial vasodilator functions during pathological development of pulmonary hypertension (PH) and right ventricular hypertrophy (RVH), we examined changes in serotonin (5-HT) removal rates and the production of prostacyclin (PGI2) and nitric oxide (NO) in isolated rat lungs harvested at various times after single exposure to monocrotaline (MCT). We assessed the generation of vasodilator substances under conditions of both the absence and the presence of 5-HT in lungs perfused with blood-free solution. Major findings included: (i) remodeling of the pulmonary vasculature associated with RVH evident 14 days after MCT injection; (ii) the capacity for 5-HT removal was suppressed at day 1 and 7 but had been restored by day 14 after MCT exposure; (iii) basal PGI2 production in the absence of 5-HT was augmented at day 1 but had returned to control levels in lungs harvested 7 or 14 days postinjection of MCT; (iv) PGI2 production evoked by 5-HT was suppressed in MCT lungs obtained at all time points examined; (v) basal NO production was suppressed at day 1 but enhanced at day 7 and 14 in MCT lungs; (vi) NO production elicited by 5-HT stimulation in 1-day-MCT lungs was obviously suppressed while that in 7- and 14-day-MCT lungs had been restored to the control level. These findings suggest that transitional changes in endothelial functions including 5-HT removal and production of vasodilators in MCT lungs do not follow the same time course.

[Role of serotonin in impaired gas exchange during pulmonary embolism].

Although serotonin has been reported to play a substantial role in cardiopulmonary dysfunction, the quantitative effects of serotonin, released from activated platelets, on the development of alveolar flooding and on impaired gas exchange in pulmonary embolism have not been systematically investigated. To elucidate the effects of serotonin on pulmonary hemodynamics, accumulation of edema fluid in alveolar space, and impairment of gas exchange in acute pulmonary embolism, 20 mongrel dogs were given 0.4-0.6 g/kg of glass beads with a diameter of 100 microns, via the internal jugular vein. Before and after embolization, pulmonary hemodynamics, systemic hemodynamics, blood gases, and the distribution of ventilation-perfusion ratios (VA/Q) in the lung were measured, with and without a newly developed selective antagonist of the serotonin S2 receptor, DV-7028. VA/Q distribution was determined by applying the multiple inert gas elimination technique. After glass-bead embolization, the animals that did not receive DV-7028 showed significant increases in pulmonary arterial pressure and in extravascular lung water, widened alveolar-arterial O2 tension differences, and appreciable development of low VA/Q areas (0 < VA/Q < or = 0.1). These changes were prevented in the animals that received DV-7028. However, DV-7028 did not affect the formation of high VA/Q areas (VA/Q > 10). In conclusion, in acute canine pulmonary embolism serotonin not only induces pulmonary hypertension and pulmonary edema, but also worsens gas exchange through the formation of low VA/Q areas.

Antitumor agents. 7. Synthesis and antitumor activity of novel hexacyclic camptothecin analogues.

Eleven novel hexacyclic and three 7,9-disubstituted pentacyclic derivatives of camptothecin were synthesized and evaluated for in vitro cytotoxic activity against P388, HOC-21, and QG-56 and in vivo antileukemic activity against P388 in mice. Hexacyclic compounds which have an additional 5-, 6-, or 7-membered ring cyclized at positions 7 and 9 of camptothecin were prepared by intramolecular cyclization of pentacyclic camptothecin derivatives or Friedländer condensation of the appropriate bicyclic amino ketone and tricyclic ketone. All of the hexacyclic compounds exhibited compatible or superior activity of 7-ethyl-10-hydroxycamptothecin (SN-38) in in vitro assays without regard to the size or type of the additional ring, and three of six compounds showed more than 300% T/C on in vivo assay. These results suggest that the potency of the hexacyclic ring system is higher than that of the original pentacyclic ring system of camptothecin and that the conformational rigidity of substituents at positions 7 and 9 is favorable for antitumor activity.

Role of 5-hydroxytryptamine in the progression of monocrotaline induced pulmonary hypertension in rats.

OBJECTIVE: The aim was to clarify the role of serotonin (5-hydroxytryptamine, 5-HT) in monocrotaline induced pulmonary hypertension. METHODS: Plasma 5-HT levels, pulmonary capillary platelet count, and vascular responsiveness to 5-HT were evaluated in the model. The effects of the selective 5-HT2 receptor antagonist, DV-7028, on the development of pulmonary hypertension were also investigated. RESULTS: Plasma 5-HT was raised 12 h to 3 d after monocrotaline administration (60 mg.kg-1), coinciding with accumulation of platelets in the pulmonary circulation. Isolated pulmonary arteries showed hyperreactivity to 5-HT at 14 and 21 d after monocrotaline. Administration of DV-7028 (20 mg.kg-1 x d-1) attenuated the increase in pulmonary arterial pressure, right ventricular hypertrophy, and medial thickening of the pulmonary arteries. CONCLUSIONS: The present study suggests that 5-HT released from platelets contributes to the initiation and progression of monocrotaline induced pulmonary hypertension.

[Roles of serotonin in glass-bead pulmonary microemboli].

We investigated the role of serotonin release from aggregating platelets in glass-bead microemboli on isolated perfused rabbit lungs. The perfusion was performed at 70 ml/min with a roller pump. The temperature of the perfusion circuit was maintained at 37 +/- 1 degrees C by means of a heat exchanger. 100 microns-diameter glass beads (1 g) were infused via the main pulmonary artery. We examined the concentration of serotonin and the number of platelets in the perfusate and the mean pulmonary arterial pressure before and after glass bead embolization. Administration of PRP (platelet-rich plasma) to the perfusate caused the concentration of serotonin to significantly increase after microembolization. Specific serotonin S2 receptor antagonist (DV-7028) inhibited the increase of serotonin concentration in the perfusate, platelet aggregation, and vasoconstriction. We concluded that in the glass-bead embolization model, serotonin was released from aggregating platelets surrounding the glass beads, and constricted pulmonary microvessels via serotonin S2 receptors on the vascular smooth muscles cells.

Combined effect of the 5-HT2 receptor antagonist DV-7028 and aspirin or heparin on coronary cyclic flow reductions in dogs.

OBJECTIVE: The aim was to study the combined effect of DV-7028, a selective 5-hydroxytryptamine2 receptor antagonist, and aspirin or heparin on cyclic flow reductions in the canine coronary artery. METHODS: Anaesthetised open chest beagle dogs under artificial respiration were used. Cyclic flow reductions were induced by partial occlusion of the left anterior descending coronary artery at the site of endothelial injury. After induction of cyclic flow reductions, test drugs were given to the animals intravenously. RESULTS: DV-7028 (0.1 mg.kg-1) reduced the frequency of cyclic flow reductions by 77% and improved the nadir of coronary blood flow velocity that indicated the severity of cyclic flow reductions. Also, aspirin (1 or 3 mg.kg-1) or heparin (200 U.kg-1) attenuated the cyclic flow reductions. In experiments with drug combinations, DV-7028 was given to animals that had already received aspirin (1 mg.kg-1) or heparin (200 U.kg-1). DV-7028 (0.1 mg.kg-1) completely abolished the cyclic flow reductions remaining after aspirin treatment in three of four animals. Heparin inhibited the cyclic flow reductions in one of five animals and the addition of DV-7028 abolished the remaining cyclic flow reductions in the other four animals. After combined injection of DV-7028 with aspirin or heparin, the coronary blood flow with cyclical reductions returned to the baseline. CONCLUSIONS: The 5-HT2 receptor antagonist DV-7028 can inhibit the cyclic flow reductions that are resistant to aspirin or heparin. The combined regimen of DV-7028 and aspirin or heparin in treatment of acute coronary stenosis is more effective than that of aspirin or heparin alone.

Pharmacological profile of a new 5-hydroxytryptamine2 receptor antagonist, DV-7028.

The pharmacological profile of DV-7028, a pyrido triazine derivative, showed that it is a potent and selective 5-hydroxytryptamine (5-HT)2 receptor antagonist. DV-7028 bound to 5-HT2 receptors in rat brain membranes with a Ki value of 22 nM and caused shifts to the right of the concentration-contraction curves to 5-HT in rat thoracic aorta and canine femoral arteries, which are attributed to activation of 5-HT2 receptors. The compound was highly active by oral administration (0.1-10 mg/kg) based on blockade of the 5-HT-induced pressor responses in pithed rats. In contrast, DV-7028 had no affinity for 5-HT1A, 5-HT1B and 5-HT1D receptors. The affinity of the compound was 14-26 times greater for the 5-HT2 receptors when compared to 5-HT1C, adrenergic alpha 1, dopamine D2 and histamine H1 receptors. In human platelets, DV-7028 attenuated the aggregation induced by collagen and inhibited the amplifying effect of 5-HT with collagen on platelet aggregation. Furthermore, a 10-day toxicity study revealed that DV-7028 was a safe compound which did not produce lethality at repeated oral doses of 800 mg/kg/day in rats. These results indicate that DV-7028 is a selective and potent 5-HT2 receptor antagonist which is orally active and safe.

Antitumor agents. V. Synthesis and antileukemic activity of E-ring-modified (RS)-camptothecin analogues.

Several E-ring-modified analogues of (RS)-camptothecin were synthesized by total synthesis via Friedländer condensation and evaluated for cytotoxicity and antitumor activity against P388 mouse leukemia cells. Among them, (RS)-20-deoxyamino-7-ethyl-10-methoxycamptothecin (25c) was found to be more active than (RS)-camptothecin (1) in the in vivo assay.

Syntheses and 5-HT2 antagonist activity of bicyclic 1,2,4-triazol-3(2H)-one and 1,3,5-triazine-2,4(3H)-dione derivatives.

A series of bicyclic 1,2,4-triazol-3(2H)-one and 1,3,5-triazine-2,4(3H)-dione derivatives with a 4-[bis(4-fluoro-phenyl)methylene]piperidine or 4-(4-fluorobenzoyl)piperidine group has been prepared and tested for 5-HT2 and alpha 1 receptor antagonist activity. Among the compounds prepared, 2-[2-[4-[bis(4-fluorophenyl)methylene]-piperidin-1-yl]ethyl]- 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one (7b) had the most potent 5-HT2 antagonist activity, which was greater than ritanserin (2), while 7b did not show alpha 1 antagonist activity in vivo. The central 5-HT2 receptor antagonism was approximately 1/30 that of 2 when tested for the ability to block head twitches induced by 5-hydroxytryptophan. Compound 21b, 3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6,7,8,9-tetrahydro- 2H- pyrido[1,2-a]-1,3,5-triazine-2,4(3H)-dione also displayed potent 5-HT2 antagonist activity. The compound had moderate alpha 1 receptor antagonism, and the potency inhibiting head twitches was about one-third that of ketanserin (1). These results indicate that 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrimidin-3(2H)-one and 6,7,8,9-tetrahydro-2H-pyrido-[1,2-a]-1,3,5-triazine-2,4(3H)-dione ring systems are useful components of 5-HT2 antagonists.

Prevention by DV-7028, a selective 5-HT2 receptor antagonist, of the formation of coronary thrombi in dogs.

STUDY OBJECTIVE: The aim was to determine the role of 5-HT derived from activated platelets in the formation of intracoronary thrombi in dogs. DESIGN: Canine coronary thrombi were produced by inserting a small catheter filled with collagen powder into the endothelial-injured partially occluded left anterior descending coronary artery. The effects of intravenous DV-7028, a selective 5-HT2 receptor antagonist (bolus of 0.1 mg.kg-1, followed by 0.3 mg.kg-1.h-1 by infusion), and intravenous aspirin (1 mg.kg-1, followed by 3 mg.kg-1.h-1) in this experimental thrombus model were examined. SUBJECTS: 43 dogs of either sex were used. In experiment A, DV-7028 (n = 12) or saline (n = 11) was given. In experiment B, aspirin (n = 10) or saline (n = 10) was given. MEASUREMENTS AND MAIN RESULTS: DV-7028 significantly reduced the formation of coronary thrombi by 51% and attenuated the decrease in coronary blood flow without affecting systemic blood pressure and heart rate. There was a significant relationship between the thrombus weight and the decrease in coronary blood flow (p less than 0.005). Aspirin failed to prevent the formation of coronary thrombi. CONCLUSION: The results suggest that 5-HT is involved in the platelet thrombosis and that inhibitory effect of DV-7028, a 5-HT2 receptor antagonist, on coronary thrombus formation was superior to that of aspirin.

[Application of the treadmill test for estimation of motor dysfunction due to pain in lumbar region and lower extremities].

Manual muscle test is one of the most reliable and objective examinations to evaluate motor dysfunction due to pain in lumbar region and lower extremities. This test is often used in the field of rehabilitation. However, it is somewhat complicated to use in general practice. Even in a pain clinic, some parts of the work are taken by these orthopedic diseases. It is thought necessary to have a convenient test to estimate the degree of motor dysfunctions. We chose the treadmill exercise test for this purpose and investigated the relationship between the manual test and treadmill test in the literature. The relationship of y = 0.85x - 185.71 was obtained and coefficient of correlation was 0.372 which is significant (P less than 0.01). On the other hand, exercise test seemed to reflect the states of recovery from disorder in each patient.

Antitumor activity of a camptothecin derivative, CPT-11, against human tumor xenografts in nude mice.

The antitumor effects of the camptothecin (CPT) derivative CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin , were tested on human tumor xenografts in nude mice. CPT-11 showed antitumor activity higher than that of Adriamycin, 5-fluorouracil, or futraful, with little or no reduction of body weight being observed in the mice. The growth of colon adenocarcinoma Co-4 was significantly inhibited after a single i.v. injection of CPT-11 at 25, 50, or 100 mg/kg. The single i.v. injection was also significantly effective against mammary carcinoma MX-1 and gastric adenocarcinoma St-15. All of the mice bearing MX-1 tumors were cured by the administration of CPT-11 every 4 days for a total of three treatments at a total dose of 200 mg/kg given i.v. or of 400 mg/kg given p.o. Three i.v. or oral treatments were also effective against Co-4, St-15, gastric adenocarcinoma SC-6, and squamous-cell lung carcinoma QG-56. To achieve the same efficacy attained by i.v. injection, however, oral doses 2-4 times higher than the i.v. doses were required. When the total dose was fixed at 100 mg/kg, a triple i.v. injection was most effective, followed by a single i.v. injection and, finally daily p.o. administration for 10 days. Although SN-38 (7-ethyl-10-hydroxycamptothecin), a metabolite of CPT-11, showed much stronger cytotoxic activity in vitro than did CPT-11, its antitumor effects were similar, if not inferior, to those of CPT-11 in vivo at the same dose level. CPT-11 was converted into SN-38 by human tumors, but the sensitivity of these tumors to CPT-11 in vivo was independent of their ability to produce SN-38. These results suggest that CPT-11 may be clinically effective, depending on the schedule of administration, but that its effectiveness is not related to the ability of the tumor to produce SN-38.

A comparison of competitive enzyme immunoassay and precipitin inhibition tests in the analysis of polysaccharide antigenic determinants of oral streptococci.

A rapid and convenient method of competitive enzyme immunoassay (EIA) was explored for the immunological analysis by MAbs of polysaccharide antigens prepared from the mutans group of streptococci, and optimal conditions for it were established. These included the concentrations of antigen, monoclonal antibodies (MAbs) and labelled antibody, temperature, pH and reaction time. The results were compared with those obtained by precipitin inhibition tests using the classical quantitative precipitin reaction, and they were found to be consistent with the latter method. It was concluded that the EIA system can be extended to the immunological study of polysaccharide antigens of oral streptococci using MAbs which perform poorly in precipitation reactions.