Two-dimensional analysis of head-shaking nystagmus in patients with Meniere's disease.

The HSN test is a simple examination that can be easily performed by clinicians, however only a few studies have analyzed the 2-dimensional characteristics of HSN in patients with MD. The objective of the study was to characterize different types of 2-dimensional head-shaking nystagmus (HSN) in patients with Meniere's disease (MD). Sixty-five patients with definite MD were enrolled. HSN was considered pathologic, if slow-phase velocity (SPV) was ≥ 4°/s and was classified as paretic or recovery according to the direction, and as monophasic or biphasic according to the presence of direction change. HSN was categorized as pure horizontal, mixed or pure vertical. When vertical SPV was larger than horizontal SPV, HSN was categorized as perverted. Forty-four patients (68%) had pathologic HSN and 28 patients (43%) had pathologic canal paresis. Monophasic-paretic HSN was the most common and followed by biphasic-paretic HSN, monophasic-recovery HSN and biphasic-recovery HSN. Delayed-peak monophasic-paretic HSN, which was not observed in vestibular neuritis, was found in 6 patients with MD. Thirty-three patients (51%) had a vertical component, which was monophasic and downbeat in 32 (97%). Every pathologic HSN in horizontal plane had higher SPV in horizontal plane than that of vertical plane. Perverted HSN was found in 4 patients, of whom 3 had pure vertical and one had mixed type HSN. Our data showed that HSN is a sensitive detector of vestibular dysfunction. HSN showed diverse types with a new type of delayed-peak HSN. Vertical components of HSN were observed in about half, but they were negligible compared to horizontal components. Weak perverted HSN (vertical SPV ≤ 4°/s) could be found in patients with MD.

Conduction Properties Of Decellularized Nerve Biomaterials.

The purpose of this study is to optimize poly(3,4,-ethylenedioxythiophene) (PEDOT) polymerization into decellular nerve scaffolding for interfacing to peripheral nerves. Our ultimate aim is to permanently implant highly conductive peripheral nerve interfaces between amputee, stump, nerve fascicles and prosthetic electronics. Decellular nerve (DN) scaffolds are an FDA approved biomaterial (Axogen ) with the flexible tensile properties needed for successful permanent coaptation to peripheral nerves. Biocompatible, electroconductive, PEDOT facilitates electrical conduction through PEDOT coated acellular muscle. New electrochemical methods were used to polymerize various PEDOT concentrations into DN scaffolds without the need for a final dehydration step. DN scaffolds were then tested for electrical impedance and charge density. PEDOT coated DN scaffold materials were also implanted as 15-20mm peripheral nerve grafts. Measurement of in-situ nerve conduction immediately followed grafting. DN showed significant improvements in impedance for dehydrated and hydrated, DN, polymerized with moderate and low PEDOT concentrations when they were compared with DN alone (a ≤ 0.05). These measurements were equivalent to those for DN with maximal PEDOT concentrations. In-situ, nerve conduction measurements demonstrated that DN alone is a poor electro-conductor while the addition of PEDOT allows DN scaffold grafts to compare favorably with the "gold standard", autograft (Table 1). Surgical handling characteristics for conductive hydrated PEDOT DN scaffolds were rated 3 (pliable) while the dehydrated models were rated 1 (very stiff) when compared with autograft ratings of 4 (normal). Low concentrations of PEDOT on DN scaffolds provided significant increases in electro active properties which were comparable to the densest PEDOT coatings. DN pliability was closely maintained by continued hydration during PEDOT electrochemical polymerization without compromising electroconductivity.

Botulinum toxin A for the management of vulvodynia.

Clinically, botulinum toxin A blocks the cholinergic innervation of the target tissue. Recently, it has been proved effective not only at a neuromuscular junction but also within parasympathetic or sympathetic neural synapses. Seven women with pain on genitalia that could not be controlled with conventional pain managements were enrolled in this study. Twenty to 40 U of botulinum toxin A were used in each injection. Injection sites were the vestibule, levator ani muscle or the perineal body. Repeat injections were administered every 2 weeks if the patient's symptoms had not fully subsided. In all patients, pain had disappeared with botulinum toxin A injections. Five patients needed to be injected twice; the other two patients needed only one injection. We did not observe complications related to botulinum toxin A injections, such as pain, hemorrhage, infection, muscle paralysis or other complications. The subjective pain score improved from 8.3 to 1.4, and no one has experienced a recurrence (the follow-up period was four to 24 months, with a mean follow-up of 11.6 months). Botulinum toxin A is effective in blocking nociception. Even though further investigation and well-controlled study will be necessary, we suggest that the botulinum toxin therapy would be useful and safe in managing vulvodynia of muscular or neuroinflammatory origins.

Effects of estrogen on nitric oxide synthase and histological composition in the rabbit clitoris and vagina.

We investigated the functional and histological changes after oophorectomy in the rabbit clitoris and vagina to determine the mechanism responsible for the development of arousal disorder in postmenopausal women. Twenty mature female New Zealand white rabbits were randomly divided into three groups: control; oophorectomy; and estrogen replacement after oophorectomy. We compared the nitric oxide synthase (NOS) activity and the degree of expression of neuronal (nNOS) and endothelial NOS (eNOS) using biochemical and Western blot analysis in clitoral and vaginal tissues. Histological change of smooth muscle and collagen contents in those tissues were also compared using Masson's trichrome staining. NOS activity and the expression of nNOS and eNOS were significantly increased in the oophorectomized group while there was a decrease to the level of the control group in the estrogen replacement group. Histological examination showed that oophorectomy induced a significant increase in collagen and decrease in muscle content in both clitoris and vagina, while the ratio of smooth muscle content was increased significantly after the estrogen replacement. Our results clearly demonstrate that estrogen deficiency induces compensatory NOS production which may be related to decreases in muscle to collagen ratio in female rabbit genital organs.

Hemodynamic insult by vascular risk factors and pharmacologic erection in men with erectile dysfunction: Doppler sonography study.

To evaluate the penodynamic impact of known vascular risk factors in men with erectile dysfunction, we obtained thorough medical histories covering diabetes, hypertension, heart disease and hypercholesterolemia, alcohol ingestion, and smoking in 265 consecutive patients. We also measured their penile hemodynamic parameters by color duplex ultrasonography after intracavernous prostaglandin E1 injection. In patients with vascular risk factors there was a statistically significant decrease in the peak systolic velocity and increase in the end-diastolic velocity of the cavernosal artery (P < 0.01). Those men who had diabetes had higher average end-diastolic velocities and lower resistance indices (P < 0.01). Smoking and alcohol use also affected penile hemodynamics (P < 0.05). These data confirm that vascular risk factors do increase the likelihood of vasculogenic impotence and that diabetes plays a major role in veno-occlusive dysfunction in the penis.

A novel function of haptoglobin: haptoglobin-haemoglobin complex induces apoptosis of hepatocarcinomatous Hep 3B cells.

Haptoglobin-haemoglobin complex (Cx) showed a cytotoxic effect on the growth of Hep 3B (human hepatocellular carcinoma) cells, dose dependently. The antiproliferative effect of Cx on the multiplication of Hep 3B cells was augmented by the presence of prostaglandin (PG) D2. Antihuman Hb IgG abolished the effect of Cx, dose-dependently, which indicates that the antiproliferative effect of Cx really is exerted by Cx. Hep 3B cells treated with Cx showed the characteristic biochemical changes of apoptosis, such as DNA fragmentation which was blocked by pretreatment with cycloheximide, and the increase of transglutaminase expression. Thus, the antiproliferative effect of Cx against Hep 3B cells occurs via the typical apoptotic pathway.

Expression and amplification of cellular oncogenes in human developing placenta and neoplastic trophoblastic tissue.

To confirm the expression of cellular oncogenes during normal development, their differential RNA levels in developing human placenta have been studied using radioactive probes such as v-abl, v-erbA, v-fms, v-mos, v-myc, N-ras and v-src. The c-mos and N-ras genes are expressed and amplified at high levels especially in term placenta, while c-abl, and c-erbA are expressed constantly during development. These findings indicate that c-mos and N-ras genes may be closely linked to normal differentiation, although c-abl and c-erbA may participate in overall developmental processes. In contrast, transcripts of c-myc and c-src are enhanced at first trimester and decreased sequentially thereafter, showing that these genes may play a role in early proliferation. Expression patterns of c-fms gene are same as that of c-myc and c-src except reelevation at term. In addition, to characterize the effect of cellular oncogene expression has been also examined in hydatidiform mole and tumor cells such as BeWo and choriocarcinoma. All cellular oncogenes examined in this study were significantly overexpressed. Thus, our results suggest that cellular oncogene activation may be strongly associated with neoplastic change of trophoblast.

Simple spectrophotometric determination of haptoglobin-haemoglobin complex in haemolysed samples.

The concentration of haptoglobin-haemoglobin complex in haemolysed serum was measured by reducing the sample with sodium hydrosulphite. The absorption spectra of serum before and after sodium hydrosulphite treatment were compared, and the absorbance change was used to determine the amount of haemoglobin in the sample. By analysing the difference absorption spectra of various types of haemoglobin-containing samples, it was also possible to determine the haptoglobin level in samples haemolysed severely beyond their haemoglobin-binding capacities. When the present methods are used, along with the spectrophotometric method for free haptoglobin, one can measure separately the amounts of free haptoglobin, haptoglobin-haemoglobin complex, and free haemoglobin in samples with varying degrees of haemolysis.

Simple spectrophotometric determination of haptoglobin level in serum.

Haptoglobin concentration was determined from the change caused in the absorption spectrum of hemoglobin due to binding with haptoglobin. Absorbance changed markedly near the Soret band, and a linear correlation could be observed between the extent of the absorbance change and the amount of free haptoglobin. The levels of serum haptoglobin measured by the present method correlated well with those determined by an electrophoretic or a peroxidase method. High concentrations (more than 10 mg/100 ml) of hematin gave positive interference in the measured haptoglobin level, whereas bilirubin and chylomicron showed low levels of interference. The proposed method could be used as a simple and reliable method for the determination of haptoglobin level in various types of sample.

Inhibition of prostaglandin synthase activity of sheep seminal vesicular gland by human serum haptoglobin.

Serum haptoglobin was added to the reaction mixture of prostaglandin synthase (EC 1.14.99.1) and its inhibitory effect was studied [1-14C]Arachidonic acid was used as substrate and the enzyme activity was estimated by monitoring the radioactivity of the products after thin layer chromatography. With or without addition of hemoglobin to the reaction mixture, both the purified haptoglobin 1-1 and 2-2 showed inhibitory activity. In the presence of 5 microM hematin, however, inhibitory activity haptoglobin was not observed. Inhibition of prostaglandin synthesis in the system depended on the molar ratio of haptoglobin to hemoglobin in the reaction mixture. These results demonstrate that haptoglobin inhibits prostaglandin synthase by restricting available heme group for the enzyme activity through complexing with hemoglobin. However, haptoglobin did not inhibit completely the stimulatory effect of free hemoglobin. Relevant significant of this effect was discussed.

Local Shwartzman-like phenomenon prepared with haptoglobin-hemoglobin complex and provoked with prostaglandin.

Intradermal injection of haptoglobin-hemoglobin (Hp-Hb) complex followed by intravenous injection of prostaglandin (PG) F2a or E2 produced a local Shwartzman-like phenomenon (LSLP) in rabbits, whereas PGE1 has no provoking action. Intradermal injection of hemoglobin or erythrocytes also produced LSLP when provoked with endotoxin or PGF2alpha. The provoking action of endotoxin in the local shwartzman reaction may not be entirely mediated through PGs.

Inhibition of the local Shwartzman reaction by turpentine, prostaglandin E2 and carbon tetrachloride.

The conventional local Shwartzman reaction (LSR) did not occur in rabbits whose plasma haptoglobin (Hp) was lowered by treatment with carbon tetrachloride, nor in animals in whom Hp was elevated after treatment with turpentine, or PGE2 or endotoxin. The possible mechanisms of such inhibition of the LSR are discussed.

An abnormal human IgA1 half-molecule.

An IgA1 half-molecule, which is composed of a deleted alpha1 chain linked with a disulfide bond to an intact kappa chain, was detected in a patient (Cha). The molecular weights of the paraprotein and the isolated alpha1 chain were estimated to be 75 000 and 53 000, respectively. Identification of tyrosine as the C-terminal amino acid and the presence of idiotypic determinants in the abnormal alpha1 chain indicated that the molecule would have an intact N-terminal variable region and a C-terminal region. Furthermore, no cleavage of the abnormal protein into Fab and Fc by proteolytic enzyme isolated from Neisseria gonorrhoeae suggested the absence of a "hinge" region in the abnormal alpha1 chain.