Intravaginal contraceptive sponge impregnated with nonoxynol-9. The development of sponge for clinical efficacy trials.

Newly designed intravaginal polyurethane sponges containing the spermicide nonoxynol-9 were developed for contraceptive purposes. The sponges were made by the polymerization of urethane monomers in a solution of nonoxynol-9. This new biomaterial is analogous to a large, thick cervical cup with a dimple in the center for ease of insertion and positioning to the cervix (and external os). There is no need for precoital planning or preparation for usage of this sponge. The release of the spermicidal agent from the sponges was 1st determined by soaking the sponges in saline and squeezing the nonoxynol-9 solution from them. In order to determine the actual amount of nonoxynol-9 released from the sponge, 2 analytic techniques were used. 1 method was ultraviolet spectoscopy and its accuracy ranged from 85-97%. The other was bioassay for the spermicidal activity and its accuracy ranged from 100-124%. To simulate the actual wearing of the sponge by a patient, the sponges were soaked in a large volume of saline and almost 50% of the spermicidal agent was released during the first 24 hours. In conjunction with the laboratory studies, a limited study to determine acceptability of the devices was investigated in normal women. The women were asked to wear the sponges for 1, 2, 3, 4, 5, 6, and 7 consecutive days. It was found that all women in the population could not tolerate the sponge longer than 5 days due to the odor. Thus, with the good release rates for 2-4 days and patient acceptability for 2 days of wear, a protocol for the use of the intravaginal sponge as a 2-day device was established. (author's)     

A case of Morgagni's hernia: availability of CT scan, ultrasonography, and trans-abdominal surgical approach

A 60-year-old obese woman was admitted to our hospital to receive surgical treatment for "slow-growing mediastinal lipoma". With the non-invasive examination such as CT scan and ultrasonography, she was revealed as Morgagni's hernia containing a greater omentum. With a trans-abdominal approach, we could take a good surgical field for the bilateral foramina of Morgagni. Several discussions were described for availability of CT scan, ultrasonography and a trans-abdominal approach.     

Development of rotary blood pump technology: past, present, and future

Even though clinical acceptance of a nonpulsatile blood flow was demonstrated almost 45 years ago, the development of a nonpulsatile blood pump was completely ignored until 20 years ago. In 1979, the first author's group demonstrated that completely pulseless animals did not exhibit any abnormal physiology if 20% higher blood flows were provided to them. However, during the next 10 years (1979-1988), minimum efforts were provided for the development of a nonpulsatile, permanently implantable cardiac prosthesis. In 1989, the first author and his team at Baylor College of Medicine initiated a developmental strategy of various types of nonpulsatile rotary blood pumps, including a 2-day rotary blood pump for cardiopulmonary bypass application, a 2 week pump for ECMO and short-term circulatory assistance, a 2 year pump as a bridge to transplantation, and a permanently implantable cardiac prosthesis. Following the design and developmental strategy established in 1989, successful development of a 2-day pump (the Nikkiso-Fairway cardiopulmonary bypass pump) in 4 years (1989-1993), a 2 week pump (Kyocera gyro G1E3 pump) in 6 years (1992-1998), and a bridge to transplant pump (DeBakey LVAD-an axial flow blood pump) in 10 years (1988-1998) was made. Currently, a permanently implantable centrifugal blood pump development program is successfully completing its initial Phase 1 program of 5 years (1995-2000). Implantation exceeded 9 months without any negative findings. An additional 5 year Phase II program (2000-2005) is expected to complete such a device that will be clinically available.     

A Question and Answer E-Mail System for Responding to Query from the General Public with Which the System Manager Can Identify Delayed Replies

We constructed a question and answer system for direct delivery of E-mail queries from the general public to the proper hospital representative and with which the system administrator can monitor E-mail replies. The system consists of two sub-systems; one is an E-mail questionnaire sub-system that automatically delivers E-mail queries to the proper person and an E-mail reply monitor sub-system with which the system administrator can monitor the E-mail replies. The monitor system compares the origin address of the E-mail reply and the destination address on a questionnaire filled out at the time the query is made. In a test of the system, 56 queries were received in 31 days, with 37 replied to. The interval from receipt of an E-mail query to reply was calculated. Nineteen replies were submitted within 2 days.     

Involvement of M3 muscarinic receptors of the spinal cord in formalin-induced nociception in mice

Subcutaneous injection of formalin into a paw of mice caused two distinct phases of licking and biting, first phase (1-5 min) and the second phase (7-30 min) after the injection. The muscarinic antagonist atropine (0.1-10 ng, i.t.) and the M(3) receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (0.1-20 ng, i.t.) inhibited the second phase of this response, whereas higher doses of atropine (20-100 ng, i.t.) did not cause inhibition. The M(1) muscarinic receptor antagonist pirenzepine (10-100 ng, i.t.) did not inhibit either the first or the second phase response, but a high dose of pirenzepine (1000 ng, i.t.) tended to inhibit the second phase response. On the other hand, the M(2) muscarinic receptor antagonist 11-?(2-[(diethylamino)methyl]-1-piperidinyl?acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one (AF-DX116; 10-1000 ng, i.t.) had no effect on either the first or the second phase of response. The opioid receptor antagonist naloxone did not affect the 4-DAMP-induced anti-nociceptive response. The i.t. injection of the acetylcholinesterase inhibitor neostigmine (25 ng) significantly inhibited only the second phase. The acetylcholine (ACh) depletor hemicholinium-3 (HC-3) (1 microg, i.t.) completely abolished the 4-DAMP-induced anti-nociceptive response. The ACh content of the spinal cord was significantly increased 14 min after formalin injection. This significant increase in the ACh content was inhibited by pretreatment with 4-DAMP (10 ng, i.t.). These results suggest that endogenous ACh in the spinal cord acts as a transmitter anti-nociception, and that ACh release regulated by presynaptic M(3) muscarinic receptors in the spinal cord is involved in the second phase of nociception induced by formalin.     

Pharmacological characterization of a novel AVP(4-9) binding site in rat hippocampus

pGlu-Asn-Cys (Cys)-Pro-Arg-Gly-NH(2) (AVP(4-9)), a major metabolite C-terminal fragment of Arginine(8)-vasopressin (AVP), improves the disruption of the learning and memory, and is a far more potent in the mnemonic function than AVP. In this study, we pharmacologically characterized its putative binding site and mechanism of intracellular signaling. Radioligand binding assay showed that [35S]AVP(4-9) could detect specific binding sites in the rat hippocampus membrane preparations, and the binding site was specifically displaced by AVP(4-9) but not by either V(1) or V(2) antagonists. Furthermore, [35S]AVP(4-9) could not detect the cloned rat V(1a), V(1b) and V(2) vasopressin receptors. Even at a low doses (10-100 pM), AVP(4-9) caused an increase in both inositol(1,4, 5)-trisphosphate (Ins(1,4,5)P(3)) and intracellular calcium concentrations ([Ca(2+)](i)) in rat hippocampal cells. The AVP(4-9)-induced [Ca(2+)](i) increase was partially inhibited by the absence of Ca(2+) or by Ca(2+)-channel blocker, suggesting that AVP(4-9) caused the [Ca(2+)](i) increase via release from intracellular calcium store as well as influx from extracellular calcium. For the first time, this study provides evidence to show that AVP(4-9) activates Ins(1,4,5)P(3)/[Ca(2+)](i) pathway through a novel type of receptor in rat hippocampus, which might be potentially important in improving the mnemonic function.     

Role of caspase-1 subfamily in cytotoxic cytokine-induced oligodendrocyte cell death

Oligodendrocytes are myelin forming cells in mammalian central nervous system. About 50% of oligodendrocytes (OLGs) undergo cell death in normal development. In addition, OLG cell deaths have been observed in demyelinating diseases including multiple sclerosis (MS). Clinical observations and in vitro cell culture studies have suggested that cytokines mediate OLG cell damage in multiple sclerosis (MS). Among the cytokines, tumor necrosis factor (TNF) is thought to be one of the mediators responsible for the damage of OLGs in MS. The administration of TNF-alpha to primary cultures of OLGs induced DNA fragmentation, and significantly decreased the number of live OLGs. Chemical inhibitors Ac-YVAD-CHO (a specific inhibitor of caspase-1 (ICE)-like proteases) enhanced the survival of TNF-alpha treated OLGs better than Ac-DEVD-CHO (a specific inhibitor of caspase-3 (CPP32)-like proteases). These results indicate that caspase-1-mediated cell-death pathway are activated in TNF-induced OLG cell death. Caspase-11 is involved in activation of caspase-1. Oligodendrocytes from caspase-11-deficient mice are partially resistant to TNF-induced OLG cell death. Our results suggest that the inhibition of caspase-1 sufamily may be a novel therapeutic approach to treat MS.     

The low prevalence of high levels of expressed emotion in Bali

The present study contrasts the expressed emotion (EE) status in family members of schizophrenic patients between Bali (Indonesia) and Tokyo (Japan), the former being a non-industrialized society and the latter an industrialized society in Asia. The EE ratings of each key relative for 62 consecutively hospitalized schizophrenic patients at the Bangli State Mental Hospital (Bali) and 33 consecutively admitted schizophrenics at Komagino Hospital (Tokyo) were obtained using the Five Minute Speech Sample (FMSS) method. A significantly lower prevalence of high EE (12.9%) was observed in Bali compared with Tokyo (36.4%) (P<0.01). This result may explain the better social adjustment of schizophrenics in Bali. In addition, in Bali, to clarify the EE effect in this non-industrialized society, we examined the relationship between each key relative's EE and the patient's psychotic symptoms at admission, as assessed by the Brief Psychiatric Rating Scale (BPRS) and the Scales for the Assessment of Negative Symptoms (SANS). Moreover, the association between each family member's EE and a patient's rate of re-admission over the 1-year period following discharge was evaluated. The EE value was significantly related to the anxious-depression factor score in the BPRS, but not to either of the other factor scores in the BPRS or SANS subscales. Furthermore, EE status was not a reliable predictor of patient re-admission over the 1-year period following discharge in Bali.     

Comparative studies on patient's and family's basic attributes, psychosocial states and treatment prognoses at three medical institutions for treatment of alcoholism]

A research by questionnaire was conducted at three medical institutions, on basic attributes and psychosocial states of alcoholics' as first time inpatient and respective families. After a year of research, additional study was conducted in regard of abstinence, treatment continuation as outpatient, participation in self-help groups, and family's participation in family groups. Outcomes of researches' statistical analyses showed significant differences concerning medical institutions and basic attributes for the items: treatment histories of alcoholism, treatment or inpatient in other medical departments and alcoholic's family history,; but these differences were considered to be associated with varied courses of referrals. In relation to medical institutions with patients and family's psychosocial states, there were no significant differences on the outcomes of five scales. As for the correlation between medical institutions with a year's prognoses there were no significant differences concerning abstinence and treatment continuation as outpatient. In case of participation in self-help groups and family groups, the prognoses showed significant differences but these differences were considered to be related to varied treatments and different helping ways of medical institutions and varied conditions of local communities for mentioned helps.