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Biomedical subjects

C Oh

Publications and source records attributed to C Oh.

At least 37 records · Page 2Linked to original sources

Anal fissure. 20-year experience.

PURPOSE: This study was designed to review a 20-year experience of the treatment of patients with anal fissure to identify possible etiologic factors and to explore effective preventative measures and the ideal treatment for this disease. METHODS: From January 1972 to December 1991, 1,391 patients (700 males, 691 females; average age, 39 years) with chronic symptomatic anal fissures underwent surgical treatment using either open or closed techniques. The following procedures were performed: 1) internal sphincterotomy for 1,313 idiopathic fissures; 2) C-anoplasty for 36 cases of anal stricture; 3) debridement and sphincterotomy for 25 patients with postsurgical nonhealing wounds; 4) bilateral excision of the protruding internal sphincter for 17 patients with "subluxation." Acute superficial anal fissures were treated conservatively, with emphasis on anal hygiene. RESULTS: Acute superficial and fissures responded well to conservative management. Over 95 percent of patients with chronic anal fissures treated by surgery had satisfactory relief of symptoms. Early complications included urinary retention (1.4 percent), bleeding (1.1 percent), and abscess and fistula formation (0.7 percent). Late complications manifested as flatus and liquid incontinence (1.5 percent), delayed wound healing (1.4 percent), recurrence of fissures (1.3 percent), and symptomatic itching and burning (1.1 percent). The complication rate was higher in the group that underwent closed sphincterotomy than in the group treated by open techniques. CONCLUSIONS: Proper and hygiene is important in both prevention and initial conservative management of symptomatic anal fissures. For chronic intractable cases, open lateral internal sphincterotomy is strongly recommended. C-anoplasty should be done when strictures are present. Excision of the protruding internal sphincter is recommended in patients who present with an excessively elongated, tight anal canal with a partially protruding internal sphincter.

Adolescent↗

A compartmental model for the ocular pharmacokinetics of cyclosporine in rabbits.

Studies were conducted in rabbits to determine the ocular distribution and elimination of cyclosporine, with the objective of developing a comprehensive pharmacokinetic model. Following a bolus dose into the anterior chamber, drug levels were measured in the aqueous humor, cornea, iris/ciliary body, lens, sclera, and conjunctiva. Cyclosporine was rapidly eliminated from the aqueous, but drug levels in ocular tissues persisted for in excess of 48 hours, particularly in the cornea and iris/ciliary body. The terminal elimination half life from these tissues was 45 hr and 30 hr, respectively, providing evidence that these tissues could act as a reservoir for the drug. It was found that a compartmental model accurately described the experimental data. A single compartment was used for each of the tissues and fluids sampled, except for the cornea, which was subdivided into two compartments, representing its tissue and aqueous regions.

Animals↗

A subconjunctival degradable implant for cyclosporine delivery in corneal transplant therapy.

The effect of local cyclosporine therapy upon corneal transplant survival was investigated. A high risk rabbit model with vascularized corneas was used to assess the efficacy of subconjunctivally implanted degradable devices for cyclosporine therapy. Animals were divided into four groups, receiving either no therapy, a placebo PLGA device, or drug containing devices implanted either at the time of transplantation or two weeks previous. The mean survival times of animals in the control and placebo groups were statistically equivalent (21 +/- 4 days vs 18 +/- 4 days). Devices containing CsA improved the survival time of grafts. Predosing the animals with CsA improved the survival time to 28 +/- 7 days, and CsA devices implanted at the time of transplantation increased the survival time to 35 +/- 7 days. The improvement in survival times was consistent with the in vitro drug release profiles. No systemic CsA was detected, suggesting that the effect may have been local. Histological assessment indicated that devices were well tolerated.

Animals↗

(-)-Deprenyl alters the survival of adult murine facial motoneurons after axotomy: increases in vulnerable C57BL strain but decreases in motor neuron degeneration mutants.

The effect of (-)-deprenyl on the survival of axotomized adult murine facial motoneurons was investigated. Previously, (-)-deprenyl was shown to increase the number of rat facial motoneurons (FMns) surviving after axotomy at postnatal day 14, apparently by compensating for the loss of muscle-derived trophic factor. In the present study, three different strains of adult mice--A/J, C57BL/6J, and a congenic substrain of the C57BL/6J mice, the C57BL/Mnd mutants--underwent unilateral facial nerve transection. FMns were counted from serial sections taken through the entire length of the facial nuclei ipsilateral and contralateral to the facial nerve transections in animals sacrificed 21 days after axotomy. Subgroups of C57BL/6J and Mnd mutants were treated with either saline or 1.0 mg/kg (-)-deprenyl for 21 days. Another subgroup of Mnd mutants were treated with the metabolites of (-)-deprenyl, a mixture of (-)-amphetamine and (-)-methamphetamine, at a dosage equimolar to 1.0 mg/kg (-)-deprenyl. The number of surviving facial motoneurons in the A/J strain was 90% of unlesioned, control values which supports previous findings that adult FMns receive adequate trophic support and thus can survive loss of muscle-derived trophic support. In the C57BL/6J strain, the facial motoneuron survival was 35% and (-)-deprenyl increased the survival to 50.5%. Mnd mutants showed 62.4% survival; however, (-)-deprenyl decreased the number of motoneurons to 54.9% and amphetamine and methamphetamine treatment further decreased the motoneuron survival to 41.1%. These findings show that FMns in the Mnd mutants and their parental strain, C57BL/6J mice, show greater vulnerability to axotomy as compared to other adult strains of mice. The vulnerability is similar to that found in early postnatal life. (-)-Deprenyl increases the survival of the axotomized C57BL/6J FMns but its major metabolites, (-)-methamphetamine and (-)-amphetamine, further decrease FMn survival in the C57BL/Mnd mutants, possibly due to the induction of neurotoxic proteins causing programmed neuronal death. The efficacy of (-)-deprenyl in increasing the survival of damaged neurons would be expected to decrease as dosage increased above the dosage sufficient to induce maximum neuronal rescue (approximately 0.01 mg/kg) but would decrease as the dosage exceeded that necessary to produce toxic concentrations of the metabolites of (-)-deprenyl (1.0 mg/kg in this study).

Amphetamine↗

Local efficacy of cyclosporine in corneal transplant therapy.

Studies were conducted to evaluate the efficacy of direct injections of cyclosporine (CsA) into the anterior chamber for the prevention of corneal allograft rejection in Dutch Belted rabbits. The mean survival time (MST) of grafts progressively increased from 50 to 89 days as the CsA concentration in the dose was increased from 1 to 10 mg/mL. Injection of 30 microL of 20 mg/mL CsA in olive oil prolonged graft survival to beyond 125 days without any signs of rejection. By comparison, the MST of allografts in control animals which received no therapy was 32 +/- 5 days, and the MST in animals administered a placebo of olive oil only was 31 +/- 4 days. The observed concentration dependence of the MST on CsA concentration is likely related to the time over which the drug delivery rate provides sufficient drug to achieve a therapeutic concentration in the aqueous humor; these studies suggest that the minimum delivery rate to the anterior chamber is between 200 and 325 ng/day. The efficacy of CsA was due to local delivery, and was likely not a systemic effect, because CsA was not detected in the systemic circulation at any time. This indicates that direct delivery of CsA to the eye can be useful in prolonging corneal graft survival, while minimizing systemic side effects. Separate experiments revealed that episodes of advanced rejection could not be reversed by a 30 microL dose of 20 mg/mL CsA to the anterior chamber, indicating the importance of avoiding long periods of subtherapeutic dosing.

Animals↗

A rate turbidimetric immunoassay for theophylline using biotin-avidin system.

We describe a biotin-avidin based rate turbidimetric homogeneous immunoassay for the determination of serum theophylline with a measuring range of 0-40 micrograms/ml. The assay features an avidin-biotin-labeled theophylline conjugate and a monoclonal antibody. The rate of change of turbidity caused by the antibody-conjugate complexing was monitored on the Beckman Synchron CX 4 System at 340 nm and 37 degrees C. Theophylline in a sample inhibited the complexation, and the extent of inhibition allowed the quantitation of theophylline in the sample. The within-run coefficient of variation (CV) was < 3.7% and the between-run CV was 5.2-9.2% depending on the theophylline concentration. Linear regression analysis showed a good correlation with an established fluorescence polarization immunoassay (r = 0.9866, n = 94).

Avidin↗

S-plasty for various anal lesions.

Ten patients underwent S-plasty between July 1979 and April 1990 for the treatment of various anal conditions. Six patients had giant condyloma acuminata, and there was one patient each with Bowen's disease, verrucous carcinoma, and stricture, and ectropion (Whitehead deformity). Both anatomic and functional results were satisfactory in all patients, and there were no serious complications. S-plasty is the preferred method for the reconstruction of extensive circular denuded anal canal with full-thickness graft of bilateral rotating skin flaps. It is important not only to construct large flaps with a good blood supply, but also to obtain complete hemostasis of the raw surface.

Anus Diseases↗

Surgical treatment of tumors of the distal rectum with sphincter preservation.

One hundred one patients with villous adenoma or invasive carcinoma of the distal rectum treated with local excision or coloanal anastomosis were studied. Twenty-three (45%) of the 51 patients with villous adenomas had transanal excision, another 23 (45%) had a posterior proctotomy, and five (10%) had a coloanal anastomosis. Only two patients with a villous adenoma developed a recurrence requiring repeat local excision. Fifteen (30%) of the 50 patients with invasive cancer were treated by transanal excision. All had tumors confined to the submucosa or superficial muscularis. Eighteen (85%) of 21 patients having posterior proctotomy also had tumors with similar depth of invasion. Six (43%) of the 14 patients having coloanal anastomosis had Dukes' B tumors, six (43%) were Dukes' C, and another two (14%) underwent palliative resection. The overall actuarial 5-year survival was 77%. Only four patients treated by transanal excision or posterior proctotomy died of metastatic disease. In the coloanal group, two of 12 patients undergoing curative resection died of recurrent cancer, and another has a pelvic recurrence. Villous adenomas of the distal rectum and selected carcinomas may be treated with local excision and coloanal anastomosis with preservation of sphincter function with good results.

Adenocarcinoma↗

Endometriosis of the perineum; report of two new cases and a review of literature.

The incidence of endometriosis at the episiotomy site is quite rare. We have experienced two cases of perineal endometriosis over a 9 year period. The typical clinical history and local findings enable us to make the correct diagnosis of both cases. The treatment of choice is complete surgical excision of endometrial tissue and usually obtains permanent cure. A review of the English literature showed there were 66 cases reported previously. The possible pathogensis of endometriosis and various modality of treatment were also discussed.

Adult↗

Intrastriatal infusions of ascorbate antagonize the behavioral response to amphetamine.

Compared to saline, bilateral infusions of ascorbate (AA) into the neostriatum of freely moving rats attenuated rearing, head bobbing, and sniffing at various times after systemic amphetamine administration. Comparable AA infusions into overlying cerebral cortex failed to alter the amphetamine behavioral response. Intrastriatal AA also enhanced the ability of haloperidol to antagonize amphetamine-induced forepaw shuffling and locomotion. Voltammetric measurements in separate animals revealed a linear increase in neostriatal AA that remained within reasonable physiological limits over the course of the AA infusion. Thus, endogenous AA may modulate behavior via mechanisms intrinsic to the neostriatum.

Administration, Intranasal↗

Possible involvement of adenosine 3':5'-cyclic monophosphate and extracellular calcium ions in histamine stimulation of interleukin-1 release from macrophage-like P388D1 cells.

Culture of macrophage-like P388D1 cells led to a spontaneous increase in release of interleukin-1 (IL-1). Addition of histamine enhanced the process as a function of its dose; histamine was effective at a concentration of as low as 10(-6)M and maximally at a dose of 10(-3)M. The effect of histamine was partially blocked by an H1-antagonist, diphenhydramine, at 10(-6)M - 10(-4)M. Ranitidine, an H2-antagonist, had no appreciable effect on the histamine-stimulated IL-1 release, even at a dose of 10(-5)M. At 10(-4)M it attenuated the histamine effect. Combination of the H1- and H2- antagonists resulted in a larger magnitude of attenuation of the histamine effect than that caused by either the H1-antagonist or the H2-antagonist alone. An H1-agonist, 2-pyridylethylamine, markedly augmented IL-1 release, reaching a maximum at 10(-4)M. Dimaprit, an H2-agonist, also stimulated IL-1 release, but the effect was far less than that of the H1 agonist. Dibutyryl adenosine 3':5'cyclic monophosphate (DBc-AMP) caused a marked rise in IL-1 production by the cells. The effects of DBc-AMP were synergistic to the effects of histamine at all doses examined. Histamine significantly augmented the uptake of 45Ca2+ by the cell as a function of time and dose of the amine. Addition of Co2+ attenuated the histamine effect at doses between 10(-5)M and 10(-4)M. These results suggest that the histamine-stimulated IL-1 release from P388D1 cells is dependent on both H1- and H2-receptors and involves both influx of calcium ions to the cells and altered intracellular concentration of adenosine 3':5'cyclic monophosphate.

Animals↗

Blockade of both D1- and D2-dopamine receptors inhibits amphetamine-induced ascorbate release in the neostriatum.

In vivo recordings with electrochemically modified microvoltammetric electrodes revealed that several neuroleptic drugs, including haloperidol, clozapine, and thioridazine, blocked the rise in extracellular ascorbate produced by amphetamine in the neostriatum of urethane-anesthetized rats. This effect was also observed in animals that received a combined injection of Sch-23390 and sulpiride, but not when either of these drugs were administered alone or in combination with the 5-HT2 blocker, ritanserin. These results indicate that a combined blockade of D1- and D2-dopamine receptors blocks amphetamine-induced ascorbate release.

Amphetamines↗

Clinical significance of rectal cancer in young patients.

Thirty-nine patients (age 40 years and younger) with rectal cancer treated at the Mount Sinai Hospital between 1967 and 1985 were studied. Their mean age was 34 years (range, 21 to 40). A positive family history for colorectal cancer was found in six patients (15 percent). Fifty percent of patients under age 30 had metastatic disease at diagnosis. Twenty-seven patients (69 percent) had potentially curative resections. Of these, 17 (63 percent) had lymph-node metastasis. This rate is twice as high as in a group of 315 patients with rectal cancer over age 40 (31 percent). The overall five-year survival for young patients having curative resection was 53 percent. Noncolorectal cancer occurred in three patients in this series and six patients also had first-degree relatives with noncolorectal cancer. Young patients with rectal cancer appear to belong to a high-risk cancer group which often seems to have a genetic pattern of predisposition.

Adult↗

Acute thrombosed external hemorrhoids.

From 1981 to 1985, 159 patients with acute thrombosed external hemorrhoids were treated by the author. This condition is relatively common in young persons; the mean age of the 159 patients in the series was 36 years. The condition was often preceded by a bout of constipation. The incidence was higher in male than in female patients, the ratio being 2:1. These hemorrhoids were slightly more prevalent on the left side (51%), whereas ordinary internal hemorrhoids tend to develop more on the right side (61%). I have postulated that the stagnation of blood and trauma to the anal vessels due to strain is the common denominator in the development of thrombosis. Therefore a rational approach to the condition is to eliminate stasis, trauma, and excess strain. Since the excess strain during defecation is usually caused by constipation, softening the stool is the key to preventing excessive strain. The condition is usually self-limiting and subsides in a few days to a week. If the condition fails to respond to conservative treatment, complete surgical excision of the thrombus is necessary.

Acute Disease↗

Reversal by ascorbic acid of suppression by endogenous histamine of rat lymphocyte blastogenesis.

Addition of concanavalin A (Con A) to a culture of spleen cells of ODS-od/od rats, which cannot synthesize ascorbic acid, increased the activity of histidine decarboxylase (HDC) in the culture, leading to accumulation of histamine (Hm) in the medium. Treatment of the culture with cimetidine, a type 2 Hm antagonist, enhanced Con A-dependent lymphocyte blastogenesis even in the absence of any exogenously added Hm. Addition of low doses of histaminase increased Con A-dependent lymphocyte transformation. At higher doses, it abrogated the reaction. At concentrations of more than 10(-10) M, exogenously added Hm suppressed the Con A-dependent uptake of [3H]thymidine by the lymphocytes, but it significantly augmented the response at 10(-14) M. The addition of ascorbic acid (10(-8)-10(-5) M) to the culture suppressed the Con A-mediated HDC induction and inhibited Hm biosynthesis. Concomitantly added ascorbic acid at the concentrations of 10(-8)-10(-4) M increased the uptake of [3H]thymidine dependent on Con A or phytohemagglutinin by the lymphocytes. These results suggest that mitogen-dependent lymphocyte blastogenesis is activated by Hm produced by the spleen cells per se. However, when culture was prolonged, high concentrations of Hm suppressed the reaction. Ascorbic acid enhances mitogen-dependent lymphocyte blastogenesis through inhibition of HDC induction, leading to attenuation of immunosuppressive Hm production by the spleen cells.

Animals↗

Inhibition by glucocorticoids of mitogen-dependent histamine biosynthesis caused by histidine decarboxylase in cultured mouse spleen cells and peritoneal adherent cells.

When spleen cells of C57BL/6 mice were cultured, their histidine decarboxylase (HDC) activity increased with a concomitant increase in the histamine concentration in the culture medium. The addition of concanavalin A (Con A) or E. coli lipopolysaccharide (LPS) to the culture enhanced the responses. Treatment with dexamethasone or corticosterone significantly inhibited both spontaneous and Con A-dependent induction of HDC and histamine biosynthesis. Progesterone and estradiol did not inhibit but rather enhanced the responses. Testosterone had little effect on HDC activity and the histamine level of the culture medium of spleen cells. Adherent cells obtained from glycogen-stimulated peritoneal exudates had the enzyme constitutively. Con A had no appreciable effect on the HDC activity and the histamine level of the culture of these adherent cells. However, the addition of conditioned medium of T + B lymphocytes that had been incubated in the presence of Con A rendered the adherent cells responsive to Con A, leading to an increase in the HDC activity and the histamine level of the culture of the cells. Treatment with dexamethasone largely abrogated the responses. The results suggest that HDC-dependent histamine biosynthesis by peritoneal adherent cells is inhibited by glucocorticoids, which act on the adherent cells per se.

Animals↗

Histamine synthesis by non-mast cells through mitogen-dependent induction of histidine decarboxylase.

Culture of spleen cells of C57BL/6 mice led to a spontaneous increase in activity of histidine decarboxylase (HDC) in the cell and the medium. Concomitantly histamine increased in the cells and, especially, in the medium. Addition of concanavalin A (Con A) or lipopolysaccharide (LPS) to the culture enhanced these processes. There was also a significant Con A-dependent increase in HDC activity and histamine biosynthesis in the culture of spleen cells of genetically mast-cell deficient W/Wv mice. Peritoneal macrophages of C57BL/6J mice had constitutively 11-19-fold as much HDC as T and B lymphocytes when compared on the basis of same number of cells. Con A had no effect on HDC activity when the macrophages were cultured alone. However, co-culture with T lymphocytes, separated from macrophages by a millipore filter membrane (pore size, 0.45 micron), rendered the macrophages responsive to Con A, leading to a notable increase in HDC activity in the cell. Addition of LPS caused a small but significant increase in HDC activity in macrophages, even when the cells were cultured alone. Co-culture with T or B cells enhanced the LPS-dependent increase in HDC activity in macrophages. In contrast, the HDC activity in T and B lymphocytes did not change essentially in the presence of any of these mitogens, even when they were co-cultured with macrophages. These results suggest that histamine is synthesized by non-mast cells through HDC.

Animals↗

Significance of increased secretion of glucocorticoids in mice and rats injected with bacterial endotoxin.

Injection of mice or rats with lipopolysaccharide (LPS) is associated with an increased secretion of glucocorticoids. The high level of mortality following injection of LPS that is noted in adrenalectomized rats can be reversed by dexamethasone or corticosterone. That histamine may be an endogenous mediator of the release of corticosterone caused by LPS is suggested by an attenuation of this corticosterone response by promethazine, an H1 antihistamine. Additional support that LPS-dependent glucocorticoid secretion is mediated, in part, by histamine, is suggested by spleen cell transfer studies revealing differences in the induction of histidine decarboxylase (HDC) synthesis and corticosterone release by the C3H/HeN and C3H/HeJ strains of mice that are differentially sensitive to LPS effects. These and other data on increased levels of histamine and HDC during mitogen-induced lymphocyte blastogenesis, as well as experiments revealing immunomodulatory effects of histamine and histamine agonists and antagonists on lymphocyte blastogenesis, are consistent with the hypothesis that following infection with gram-negative bacteria, the histamine-induced increase in glucocorticoid secretion results in inhibition of HDC in splenocytes, a concomitant attenuation of histamine production, and a resulting return to immune homeostasis.

Animals↗