Differential physiologic effects of perfusion of scala tympani versus scala vestibuli in the ischemic cochlea.

The effectiveness of perilymphatic perfusion with oxygenated artificial media upon the endocochlear potential (EP) was measured during systemic ischemia in the guinea pig. Differences in the effects of perfusion of the two perilymphatic scalae were determined. Perfusion of scala vestibuli with oxygenated artificial perilymph at a high flow rate resulted in complete recovery of the EP to the pre-ischemic level, whereas perfusion of scala tympani with the same medium was unable to effect complete recovery. The recovery obtained by perfusion of scala tympani was about half that obtained of scala vestibuli. The pO2 in scala media was measured during perfusion by means of oxygen-sensitive microelectrodes. perfusion of scala vestibuli led to an approximately two-fold higher pO2 in scala media than perfusion of scala tympani. During perfusion, the pO2 in scala media varied dependent upon depth of electrode insertion, with a gradient decreasing toward the stria vascularis, a direction opposite to that seen under normal metabolic conditions. These findings suggest that, in the ischemic cochlea, oxygen enters scala media more easily from scala vestibuli across Reissner's membrane than from scala tympani via the basilar membrane/organ of Corti complex.

Pigmentary demarcation lines of pregnancy with erythema.

We describe two patients with pregnancy-associated pigmentary demarcation lines overlapped by erythematous changes. In both cases, there was a symmetrical well-defined erythematous pigmentation involving the buttocks and flexor aspects of the legs. After normal delivery the erythema disappeared within 7-10 days, followed by slow resolution of the pigmentation. Compression by the enlarged uterus of peripheral nerves issuing at S1-S2 is proposed as a mechanism of these changes.

Juvenile generalized pustular psoriasis in a pair of monozygotic twins presenting strikingly similar clinical courses.

We describe an exceptionally rare case of juvenile generalized pustular psoriasis noted in monozygotic twins who, after developing the disease on the same day (the 48th day after birth) continued to show strikingly similar clinical features of generalized pustular psoriasis for 7 years. Not even therapeutic intervention by tonsillectomy performed at age 4 years on one of the twins, which was expected to have some beneficial effect, could decrease the number of attacks or pustulation compared with the counterpart.

Autologous mixed lymphocyte reaction is reduced in patients with psoriasis.

The autologous mixed lymphocyte reaction (auto-MLR) was studied to test the interactions between immunocompetent cells in patients with psoriasis. The auto-MLR in 20 patients with psoriasis was significantly lower than in 16 normal controls. Lower values were found in untreated psoriatic patients than in those in remission following treatment. The values in the latter group were significantly lower than in controls and in six patients with atopic dermatitis in remission. The tendency for an increase in the auto-MLR with a decrease in disease activity was further confirmed in five patients studied before and after treatment. In contrast, the allogeneic lymphocyte reaction (allo-MLR) in psoriatics was similar to that in normal controls.

Contact sensitivity to Pityrosporum ovale in patients with atopic dermatitis.

Contact sensitivity and immediate hypersensitivity to extracts from Pityrosporum ovale were studied in patients with atopic dermatitis (AD). In a chamber-scarification patch test, 75 (64%) of 118 patients with AD responded positively, compared with 1 (3%) of 35 healthy volunteers. However, no significant statistical correlations were found between contact sensitivity to P ovale in patients with AD and any of the following factors: age, sex, distribution of skin lesions, presence of pruriginous papules, history of infantile seborrheic dermatitis, or concomitance of other atopic diseases. Lymphocyte transformation test with P ovale antigen confirmed that those with positive patch test reactions showed significantly high stimulation indexes. The antigenic substances divided by gel filtration high-performance liquid chromatography were found in a fraction of components with molecular weights above 60 kd. In addition, 25 (71%) of 35 patients with AD showed a positive immediate response to P ovale extract in a prick test, whereas none of 11 healthy volunteers showed any response. Although the incidence of the positive immediate responses was similar to that in contact sensitivity, there was no clear correlation between the delayed and immediate hypersensitivity reactions. Based on these results, we think that P ovale plays a role as an allergen derived from the host environment in the exacerbation of the skin lesions of AD.

Analysis of the proinflammatory property of epidermal cyst contents: chemotactic C5a anaphylatoxin generation.

We investigated in vitro the contents of epidermal cysts for complement activation and found that they activated complement mainly through the alternative pathway. Chemotactic C5a anaphylatoxin produced by the cyst contents after contact with serum most likely plays a significant role in the initiation and aggravation of inflammation in ruptured epidermal cysts. Our additional study disclosed that components of three representative follicular resident microorganisms (Pityrosporum ovale, Propionibacterium acnes, and Staphylococcus epidermidis) also produced C5a anaphylatoxin mainly through the alternative pathway; the C5a production was more vigorous than that by a virulent pathogen, Staphylococcus aureus. These results suggest that accidental colonization of the cyst contents by these follicular microbial flora further augments the inflammatory changes in ruptured epidermal cysts.

Time-related changes in cochlear potentials in guinea pigs with experimentally induced endolymphatic hydrops.

In order to examine the changes in cochlear function occurring in hydropic ears over time, endolymphatic hydrops was provoked by obliterating the endolymphatic sac in 62 albino guinea pigs. Cochlear potentials (EP, CM, SP and AP) were recorded in the 1st, 2nd, 4th and 12th postoperative weeks, respectively. A significant reduction in the level of EP was already observed in the 2nd week and the potential was further suppressed by the 4th week. There was no significant difference between the levels of the 4th and 12th weeks. The amplitudes of CM and AP decreased progressively as time elapsed after the surgery. In sharp contrast to the other potentials, the abnormality in SP was most frequently observed in the 1st week. These results are discussed in the light of the available literature.

Successful treatment of psoriasis with topical application of active vitamin D3 analogue, 1 alpha,24-dihydroxycholecalciferol.

We treated 11 psoriatic patients with topical 1 alpha,24-dihydroxycholecalciferol, a new synthetic analogue of active vitamin D3. In 10 of 15 tests the lesions cleared completely within 1-4 weeks, although some relapses occurred shortly after cessation of treatment. There were no side-effects. We suggest that 1 alpha, 24(OH)2D3 merits further investigation as a potentially useful topical therapy for psoriasis.

Immunohistologic analysis of the phenomenon of spontaneous regression of numerous flat warts.

Among various tumors induced by human papilloma virus (HPV), flat warts are unique in that they show a systemic regression phenomenon after sudden occurrence of inflammation in all the tumors, leaving permanent immunity to flat warts in the host. When studied immunohistochemically, the presence of HPV antigen using papilloma virus genus-specific antiserum in 31 cases of regressing flat warts was not found; whereas it was demonstrated in the nuclei of upper epidermal cells of ordinary flat warts in 12 of 19 cases (63%). T-cell phenotype assessment in nine regressing flat warts using monoclonal antibodies showed that helper/inducer subsets constituted a major peritumoral dermal infiltrate with a moderate number of intermingling OKT6+ cells. In contrast, the tumoral epidermis was invaded by almost equal number of suppressor/cytotoxic T-cells and helper/inducer T-cells, where at least some keratinocytes also expressed HLA-DR antigen in addition to Langerhans cells. Most T-cells expressed HLA-DR antigen, a marker of activation, but only a small number of them were Tac antigen+, i.e., bearing interleukin 2 receptors. Leu 7+ natural killer cells were seldom found in the infiltrate. These data provide evidence that T-cell-mediated immune attack against tumor cells and not against intranuclear HPV antigen, induces the systemic spontaneous regression of numerous flat warts in humans.

Saccular and cochlear endolymphatic potentials in experimentally induced endolymphatic hydrops of guinea pigs.

Saccular and cochlear endolymphatic potentials (SEP and CEP) were recorded in 33 normal animals. We confirmed that SEP is not produced in the saccule per se, but is a potential leak from the cochlea. CEP was reduced to one-tenth of the original value when it reached the saccule. Endolymphatic hydrops was provoked in 32 animals, and CEP and SEP were successfully recorded in 29 and 20 cases, respectively. The measurements were performed in the 2nd, 4th and 12th postoperative week. Both CEP and SEP decreased in magnitude as time elapsed after the surgery. This reduction is attributed to the strial dysfunction. In advanced hydrops, CEP transmission to the saccule is greatly inhibited. It is concluded that the saccular dysfunction can occur in the hydropic ear.

Effects of barium and ion substitutions in artificial blood on endocochlear potential.

Previously, a qualitative assessment was made (Marcus, D.C. (1984): Am. J. Physiol. 247, C240-C246) of the ion-selective properties of the cells bounding the cochlear duct by observing the effects of ion substitutions in the perilymph on the transepithelial potential difference (endocochlear potential; EP). Contributions by the marginal cells of the stria vascularis to the observed changes in the EP may have been masked, however, due to their 'isolation' from the perilymph by a continuous layer of basal cells. Since the ionic milieu of the basolateral membranes of the marginal cells is controlled more directly by the blood supply than by the perilymph, we report here on the effects of ion substitutions via vascular perfusion. Elevated K (substituted for Na or N-methyl-D-glucamine; NMDG) or Ba caused marked depression of the EP. Decreased Na or Cl (replaced by NMDG and gluconate, respectively) also depressed the EP. These changes in the EP were distinctly different from those observed previously by perilymphatic perfusion, and were interpreted in terms of a modified model of the strial marginal cells.

Pathophysiology of otitis media with effusion: clinical evaluation through some qualitative methods.

In an attempt to elucidate the pathophysiology of otitis media with effusion (OME), systematic clinical investigations were undertaken. The high resolution computed tomography, tympanogram, tubal inflation and our qualitative tubal functioning test were routinely applied to cases of OME, both in children and adults. Through these studies, following was concluded: 1. The primary pathology involved may be obstructive lesion somewhere in the tubotympanic cleft including the epitympanum and the mastoid, which in turn results in negative pressure in the middle ear. 2. This negative middle ear pressure may mainly constitute the Eustachian tube dysfunction, which is considered to play an important role in the pathogenesis of OME. Discussed in detail further will be the importance of correcting the negative middle ear pressure substantially for the treatment of OME, and also the essence of our qualitative tubal functioning test.

Effect of kainic acid upon N1 latency.

Although the N1 latency of whole nerve action potential is one of the important pieces of information obtained from ECochG, there are some conflicting opinions as to whether or not it is prolonged in sensorineural hearing loss. Kainic acid (KA) is known to destroy neurons selectively through an action at glutamatergic synapses. Therefore, a model of "neural deafness" was made by perfusing the scala tympani with KA solution. The effect of KA upon cochlear microphonics was minimal. Although the N1 amplitude was markedly suppressed by KA, the N1 latency was neither prolonged nor shortened. The result obtained in the present study strongly suggests that the N1 latency is not prolonged in "neural deafness."

Support of cochlear metabolic and ion transport processes solely by perilymphatic perfusion.

Morphologic considerations would seem to suggest that the cochlear duct could not be maintained in a fully functional state in the absence of a blood supply. We found, however, that perilymphatic perfusion could be used as a substitute for the normal vascular circulation. The criteria used to determine cochlear function included (1) normal endocochlear potential, (2) normal net secretory flux of rubidium (as a tracer for K), and (3) normal levels of ATP in both the organ of Corti and the stria vascularis. All criteria were satisfied by our perfusion regimen.

Prolonged maintenance of endocochlear potential by vascular perfusion with media devoid of oxygen carriers.

A method is described for maintaining the cochlear potentials of the guinea pig via arterial perfusion of the surviving inner ear with an artificial medium devoid of oxygen carriers or oncotic agents. The endocochlear potential (EP) can be maintained at a normal level for periods in excess of 5 h; the responses of the EP to anoxia and to furosemide closely approximate those seen in the intact animal. This preparation may represent a simplified method for carrying out selected arterial perfusion experiments in the surviving inner ear.