A Study of Fluoxetine in Obese Elderly Patients with Type 2 Diabetes

In order to establish the safety and efficacy of fluoxetine in subjects over 60 years of age with Type 2 diabetes, a randomized, double-blind, parallel study of 30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily with placebo. Subjects were diet controlled with an HbA₁ < 14% (reference range 6–9%) and BMI > 29 kg m². Those taking fluoxetine had a median weight loss of 2.6 kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0–02), compared with weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months, respectively. Improved glycaemic control was also demonstrated in the fluoxetine group compared with placebo, initial HbA₁ levels of 8.0% vs 8.7% (NS) falling at 4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained improvement in fasting blood glucose levels was demonstrated. Reporting of adverse events was similar in both groups. Fluoxetine in the short term aids weight loss and improves glycaemic control without a significant increase in adverse events in elderly Type 2 diabetic subjects.     

Granular cell abrikossoff tumours of the larynx and tongue treated with the carbon dioxide (CO2) laser

Seven cases of granular cell Abrikossoff tumours of the larynx and tongue are reported: four in the tongue and three in the larynx. All of these tumours were removed with the carbon dioxide (CO₂) laser. The anatomical site of the origin and clinical features of granular cell tumours (GCT) are not specific. Histological, light microscopic, electron microscopic (EM) and immunohistochemical studies are required for diagnosis. The histogenesis and cellular derivation of GCTs is still controversial. The biological potential and lack of cellular atypia define a benign process. However, it is important to take into account that these tumours have ill-defined borders without a capsule. Radiation therapy has proved ineffective in the past. Surgical excision with a wide margin is required. Because of numerous advantages, for example, no bleeding, no oedema, minimal pain and quick recovery, CO₂ laser removal is the treatment of choice. The authors have not seen any recurrence or complications.     

CO2激光治疗喉气管狭窄的应用

为探索喉气管狭窄松解瘢痕组织的方法，近四年来，对七例严重的喉气管狭窄病人进行开放性“Ｔ”型硅胶管置入术，术中应用ＣＯ２激光切除、松解瘢痕组织，所有病人术后８～１２月成功拔管。证明ＣＯ２激光为喉气管狭窄重建术的一种有效辅助治疗手段     

LAK/IL-2联合应用治疗晚期肺癌的临床研究

选择４６例晚期肺癌患者应用ＬＡＫ／ＩＬ－２疗法观察患者近期临床改善情况及治疗前后其免疫指标的变化情况。选择胎儿胸腺淋巴组织作前体细胞，体外用重组ＩＬ－２诱导制备ＬＡＫ细胞，每输３次ＬＡＫ细胞为１疗程，每次输入细胞数为０５×１０９，化疗以采用丝裂霉素、长春新碱、顺铂或卡铂、鬼臼乙叉甙为主的方案，治疗结果：本组患者治疗有效率（ＣＲ＋ＰＲ）达７０％，同时患者免疫指标好转。本研究提示ＬＡＫ／ＩＬ－２联合疗法临床近期疗效较满意，同时可显著改善机体免疫功能，是晚期肺癌患者一种可行的有效方法     

Polycystic kidney disease genes and polycystins

Conclusion The past decade has seen extraordinary progress in the study of autosomal-dominant polycystic kidney disease. The 2 major genes for this disorder have been identified. Animal models of ADPKD have been produced. The molecular basis of the disease has been characterized. ADPKD is a “second-hit” disease, much like many cancer predisposition syndromes. This has profound implications for our understanding. The progression of ADPKD in individual patients is likely related more to their individual rate of acquisition of second hits at thePKD1 orPKD2 locus than to the inherited germ line mutation itself. Therapeutic approaches will perhaps now be considered, which will include interventions that may limit the rate at which somatic mutations occur in the kidney. The major focus of research at present is to elucidate the normal functions ofPKD1 andPKD2. Protein binding partners are being sought for both proteins. The possible calcium channel function ofPKD2 is being investigated. The downstream effects of cellular deficiency of either protein are likely to yield many clues. Modifying genetic factors that may independently affect disease progression are likely to be identified using the several mouse models. Perhaps the next decade will bring great strides in understanding and in potential therapy for this common disease. This paper was presented at the 2nd International Forum “The Frontiers of Nephrology,” Tokyo, May 10, 1998.     

PAF antagonistic activity of 2-hydroxy-3-methoxybenzoic acid glucose ester fromGentiana scabra

In order to find out anti-platelet activating factor (PAF) from natural resources, Korean medicinal plants used for the treatments of peripheral circulation disorders were tested for their possible protective effects on PAF-induced anaphylactic shock. From the above screening, the methanol extract ofGentiana scabra showed a potent antagonistic activity against PAF. Water suspension of the extract was partitioned with CH₂Cl₂ and EtOAc, successively. The EtOAc fraction which showed the highest activity was chromatographed on silica gel to yield 6 fractions. From the fraction which showed higher PAF-antagonistic activity than the other fractions, compound1 was isolated by recrystallization. On the basis of spectral data, compound1 was identified as 2-hydroxy-3-methoxybenzoic acid glucose ester. The compound prevented the mice from the PAF-induced death at a dose of 300 μg/mouse.     

Prostaglandin D2 measurement in nasal secretions is not a reliable marker for mast cell activation in atopic patients

Background Prosia gland in D2 (PGD2) is a very important mast cell product during the early-phase nasal allergic reaction. However, the quantification of PGD2 in nasal secretions has not yet been well established. Objective Quantitative determination of PGD2 in nasal secretions of atopic patients (n=17) after nasal allergen challenge (NAC) and in non-allergic healthy volunteers (n=10). Methods The nasal microsuction sampling technique was used to obtain the nasal secretions with an exactly known and minimally diluted volume. A sensitive and specific enzyme immunoassay was chosen to measure the more stable 11-methoxime derivative of PGD2. which was obtained after extraction in acelone/ethanol and conversion using methoxamine-HCl. The concentrations of PGD2 in nasal secretions obtained from 10 non-allergic healthy volunteers were used as reference values. Results There was no significant difference in the concentrations of PGD2 between men (median: 569pg/mL) and women (median: 407pg/mL), nor between the baseline concentrations from atopic patients (median: 410pg/mL) and non-allergic controls (median: 477 pg/mL). In the atopic patient group, PGD2 did not significantly increase during the entire sampling period after NAC. The absence of PGD2 response contrasted with the nasal symptoms manifested by sneezing, increased nasal airway resistance, and the significant increases of the concentrations of histamine, tryptase, and leukotriene C4 (LTC4) 5min after NAC. Conclusion This observation suggests that the measurement of PGD2 alone in the nasal secretions does not give reliable information on mast cell activation during a nasal allergic reaction.     

The nephrotoxicity and hepatotoxicity of 1,1,2,2-tetrafluoroethyl-L-cysteine in the rat

Recent studies have shown that tetrafluoroethylene is a renal and hepatic carcinogen in the rat. In this study, we have examined the ability of a single i.p. dose of 1,1,2,2-tetrafluoroethyl-l-cysteine (TFEC), a major metabolite of tetrafluoroethylene, to produce hepatic and renal injury in male and female rats. We have also examined the effect of blocking the renal organic anion transport system with probenecid and of inhibiting the activity of cysteine conjugate β-lyase with aminooxyacetic acid on the extent of renal injury produced by TFEC. Doses of ≥12.5 mg/kg TFEC produced renal tubular necrosis to the pars recta of the proximal tubules within 24 h in both male and female rats. This was associated with an increased kidney to body weight ratio and plasma urea at doses of ≥25 mg/kg. No consistent evidence of liver injury was seen at doses up to 50 mg/kg TFEC in rats of either sex, although occasional vacuolation of hepatocytes and a small dose-related increase in liver to body weight ratio was observed. Prior treatment of female rats with probenecid completely prevented the renal injury produced by either 25 or 50 mg/kg TFEC as judged by plasma urea and histopathology. However, prior treatment of female rats with aminooxyacetic acid afforded no protection against the nephrotoxicity produced by either TFEC or the cysteine conjugate of hexachloro-1,3-butadiene. Thus no major sex difference in nephrotoxicity in the rat was seen with TFEC, while accumulation of TFEC, or its N-acetyl derived metabolite, into renal proximal tubular cells via a probenecid sensitive transport system appears to be a key event in the mechanism of nephrotoxicity. The lack of protection observed with the cysteine conjugate β-lyase inhibitor, aminooxyacetic acid, may reflect the inability to completely inhibit the mitochondrial form of this enzyme and thereby prevent the formation of the reactive metabolite. Our acute studies provide no insight concerning the liver carcinogenicity of tetrafluoroethylene. Received: 8 December 1997 / Accepted: 3 February 1998     

Effect of β-endorphin on the contractile responses in mouse skeletal muscle

Tension development in response to direct and indirect electrical stimulation was studied in an isolated phrenic nerve hemidiaphragm preparation of the mouse. β-Endorphin (β-EP) caused an increase in the preparation of the mouse. β-Endorphin (β-EP) caused an increase in the response to low frequency stimulation of the nerve. Upon direct stimulation of the muscle the peptide had no effect. The actions of β-EP were abolished in the presence of the opioid antagonist naloxone and mimicked by β opioid agonists. Upon high frequency stimulation of the nerve, β-EP caused an increase in the initial, maximum, and mean tension. It also prevented the fall in the final tension seen in the control preparations with repeated periods of stimulation. The findings are consistent with β-EP having a role to improve neuromuscular function and deley fatigue, and indicate the possible therapeutic potential of opioid substances in conditions where muscle weakness is present. © John Wiley & Sons, Inc.     

Correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia

We studied the correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia. In 30 neurosurgical patients aged 40–70 years, anesthesia was induced with midazolam and sevoflurane and maintained with sevoflurane and nitrous oxide in oxygen. Serum and urine inorganic fluoride (F⁻) levels and β₂-microglobulin (BMG), blood urea nitrogen (BUN), and serum creatinine (Cr) were measured during and after anesthesia. The decrease rate of serum F⁻ level and the area under the curve (AUC) of serum F⁻ were calculated. Correlations among sevoflurane dosage, duration of administration, peak serum F⁻ level, AUC, the decrease rate of serum F⁻ level, and the maximum values in BUN, Cr, and urine BMG during the study were investigated. Urine BMG increased significantly after surgery but returned to the preoperative level in a week. BUN, Cr, and serum BMG remained within normal ranges during the study. Sevoflurane dosage and duration of administration were significantly correlated with AUC and the maximum value of urine BMG, but not with the peak serum F⁻ level or the decrease rate of serum F⁻. AUC was significantly correlated with the maximum value of urine BMG. In sevoflurane anesthesia, sevoflurane dosage, duration of administration, and AUC affected urine BMG level, but not peak serum F⁻.