Endolymphatic sac-vein decompression for intractable Meniere's disease: long term treatment results.

OBJECTIVES: We sought to determine the long-term efficacy of endolymphatic sac-vein decompression surgery on patients with classic Meniere's disease. STUDY DESIGN AND SETTING: Using the 1995 American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium criteria, starting stage, functional level, vertigo class, and hearing results were addressed. We studied 68 patients with classic Meniere's disease from a tertiary, private otology-neurotology practice. Patient data were gathered by retrospective chart review, questionnaire, and patient interview. All patients underwent endolymphatic sac-vein decompression with an average follow-up period of 55 months. RESULTS: Median functional level before surgery was level 4, improving to level 2 after surgery. Eighty-one percent of patients showed improvement in functional level, 12% remained stable, and 7% declined. Long-term vertigo control was 47% in class A, 25% in class B, 9% in class C, 3% in class D, and 16% in class F. Twenty percent of patients were in hearing stage I Meniere's disease; 31%, stage II; 44%, stage III; and 5%, stage IV. Eighteen percent of patients showed improvement in hearing class, 64% were stable, and 18% declined. CONCLUSION: Endolymphatic sac-vein decompression surgery is a safe, nondestructive surgical option for Meniere's disease that offers durable control of vertigo and stabilization of hearing for the majority of symptomatic patients. SIGNIFICANCE: The beneficial long-term outcome of the endolymphatic sac-vein decompression supports its continued use as a first-line treatment option in intractable Meniere's disease.     

Oral pilocarpine HCl stimulates labial (minor) salivary gland flow in patients with Sjögren's syndrome

Pilocarpine HCl has been shown to stimulate parotid and submandibular gland salivary flow. The purpose of this study was to determine whether this cholinergic-muscarinic drug also stimulates labial (minor) salivary gland (LSG) flow and to relate that with whole unstimulated salivary (WUS) flow rateS. Subjects diagnosed with primary Sjögren's syndrome (SS-1; n = 9) or secondary Sjögren's syndrome (SS-2; n = 9) were enrolled in this study after meeting stringent enrollment criteria. An age-gender matched control group was also enrolled. The labial saliva was collected in a standardized manner on Per-iopaper® for 5 min and the volume was analysed by the Periotron®.Whole unstimulated salivary samples were collected for 5 min by the method of Mandel and Wot-man (1976).Each subject was dosed with pilocarpine HCl (5 mg; tablets; p.o.).After 60 min the LSG flow as well as the WUS flow was determined again as previously. The results indicated a significant (>180%) increase in both labial salivary gland flow as well as whole salivary flow in the SS-1 and SS-2 subjects (mean ± S. e.m.): [SS-1: WUS = 0.1080 ± 0.03 vs 0.2242 ± 0.03 ml per 5 min; LSG = 93.1 ± 22.2 vs 167.8 ± 15.9 μl/5 min; P < 0.001; SS-2: WUS = 0.1384 ± 0.02 vs 0.2775 ± 0.09 ml per 5 min; LSG = 97.7 ± 20.2 vs 182.8 ± 17.9 μl per 5 min; P < 0.001]. These results indicate a significant increase in labial salivary gland flow as well as whole salivary flow as stimulated by pilocarpine HCI in Sjögren's syndrome patients.     

Steroid withdrawal at 3 months after kidney transplantation: a comparison of two tacrolimus-based regimens

The 6 month prospective, randomized study compared the steroid-sparing potential of two tacrolimus-based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid-resistant acute rejection and with serum creatinine concentrations <160 micromol/l. The incidence of biopsy-confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4-6 was low in all groups, both for patients on steroid-free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid-free patients with month 6 median serum creatinine levels of 119.5 micromol/l (Tac/MMF), and 115.1 micromol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 micromol/l (Tac/MMF/S) and 132.8 micromol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus-based regimens allowed the safe discontinuation of steroids in low-risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.     

Quantitative and qualitative assessment of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T cell immunity to gag in HIV-1-infected individuals with differential disease progression: reciprocal interferon-gamma and interleukin-10 responses.

The human immunodeficiency virus type 1 (HIV-1)-specific CD4(+) T cell response was investigated in 33 untreated HIV-1-infected individuals, using highly sensitive ELISPOT assays and intracellular flow cytometry. The median frequencies of interferon (IFN)-gamma-producing HIV-1 gag-specific CD4(+) T cells did not correlate significantly with control of viral replication or progression. HIV-1 gag-specific interleukin (IL)-4-producing cells were rarely detected. Circulating frequencies of CD4(+) T cells constitutively producing IL-10, however, were significantly higher in individuals with progression or active replication. In 17 of 30 HIV-1-infected individuals, gag antigen was observed to induce IL-10 production from CD4(+) T cells. In 2 individuals, early treatment of acute HIV-1 infection "rescued" low to undetectable gag-specific IFN-gamma-producing CD4(+) T cell responses and dramatically down-regulated constitutive IL-10 production from circulating CD4(+) T cells. The detection of HIV-1-specific IL-10-inducing CD4(+) T cells in HIV-1-infected individuals suggests that HIV-1 may directly subvert specific immune responses by IL-10 induction.     

Calcium blocker diltiazem inhibits platelet activation and stimulates vascular prostacyclin synthesis

The effects of slow channel calcium blocker diltiazem on platelet aggregation and on the generation of vasoactive prostanoids, thromboxane A2 and prostacyclin were examined. Diltiazem, in therapeutic concentrations (50-200 ng/ml), inhibited human platelet activation induced by cumulative subthreshold concentrations of calcium ionophore A 23187 plus ADP or epinephrine. However, platelet activation induced by cumulative effects of ADP plus epinephrine was inhibited by diltiazem only in very high concentrations (greater than 5 micrograms/ml). These data indicate that platelet aggregation mediated only through calcium flux is inhibited by diltiazem in therapeutic concentrations. In other experiments, diltiazem significantly potentiated prostacyclin release from human umbilical veins. These effects of diltiazem may contribute to efficacy of this compound in ischemic heart disease.