Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer.

BACKGROUND: We compared late thoracic radiotherapy (TRT) with early TRT in the treatment of limited-disease small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS: Patients with LD-SCLC received four cycles of etoposide plus cisplatin every 21 days. Patients were randomly assigned to receive either TRT administered concurrently with the first cycle (early TRT) or the third cycle (late TRT) of chemotherapy. The primary end point was complete response rate. RESULTS: Two hundred twenty-two patients were randomly assigned.Late TRT was not inferior to early TRT in terms of the complete response rate (early v late; 36.0% v 38.0%). Other efficacy measures including overall survival [median, 24.1 v 26.8 months;hazard ratio (HR) 0.93; 95% CI = 0.67­1.29] and progression free survival (median, 12.4 v 11.2 months; HR 1.09; 95%CI = 0.80­1.48) were not different between two arms. No statistical difference was noted in the pattern of treatment failures.However, neutropenic fever occurred more commonly in the early TRT arm than the late TRT arm (21.6% v 10.2%; P = 0.02) [corrected]. CONCLUSION: In LD-SCLC treatment, TRT starting in the third cycle of chemotherapy seemed to be noninferior to early TRT, and had a more favorable profile with regard to neutropenic fever.

Superiority of conventional intensity-modulated radiotherapy over helical tomotherapy in locally advanced non-small cell lung cancer. A comparative plan analysis.

PURPOSE: To compare helical tomotherapy (HT) and conventional intensity-modulated radiotherapy (IMRT) using a variety of dosimetric and radiobiologic indexes in patients with locally advanced non-small cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: A total of 20 patients with LA-NSCLC were enrolled. IMRT plans with 4-6 coplanar beams and HT plans were generated for each patient. Dose distributions and dosimetric indexes for the tumors and critical structures were computed for both plans and compared. RESULTS: Both modalities created highly conformal plans. They did not differ in the volumes of lung exposed to > 20 Gy of radiation. The average mean lung dose, volume receiving ≥ 30 Gy, and volume receiving ≥ 10 Gy in HT planning were 18.3 Gy, 18.5%, and 57.1%, respectively, compared to 19.4 Gy, 25.4%, and 48.9%, respectively, with IMRT (p = 0.004, p < 0.001, and p < 0.001). The differences between HT and IMRT in lung volume receiving ≥ 10-20 Gy increased significantly as the planning target volume (PTV) increased. For 6 patients who had PTV greater than 700 cm(3), IMRT was superior to HT for 5 patients in terms of lung volume receiving ≥ 5-20 Gy. The integral dose to the entire thorax in HT plans was significantly higher than in IMRT plans. CONCLUSION: HT gave significantly better control of mean lung dose and volume receiving ≥ 30-40 Gy, whereas IMRT provided better control of the lung volume receiving ≥ 5-15 Gy and the integral dose to entire thorax. In most patients with PTV greater than 700 cm(3), IMRT was superior to HT in terms of lung volume receiving ≥ 5-20 Gy. It is therefore advised that caution should be exercised when planning LA-NSCLC using HT.

Microencapsulation of rosmarinic acid using polycaprolactone and various surfactants.

Rosmarinic acid (RA) has a number of interesting biological activities, e.g. anti-viral, anti-bacterial, anti-inflammatory and antioxidant. The antioxidant activity of RA is stronger than that of vitamin E. Despite its strong antioxidant activity, it was limited to use in cosmetics because of the low water solubility, discolouration and chemical instability. The purpose of this study was to prepare RA-loaded polycaprolactone (PCL) microspheres using emulsion solvent evaporation method and characterize them with different surfactants used in the formation process. Finally, long-term stability of RA was evaluated in the cosmetic formulation. As a result, PCL microspheres were found to be spherical in shape, with zwitterionic surfactant-PCL particles being the smallest size distribution and highest entrapment efficiency of RA. Emulsions containing RA-loaded PCL microspheres showed a better long-term stability of the RA compared with those containing only RA. These results suggest that RA may be stably and efficiently encapsulated into polycaprolactone microspheres.

Inhibitory effects of antioxidant constituents from Melothria heterophylla on matrix metalloproteinase-1 expression in UVA-irradiated human dermal fibroblasts.

Matrix metalloproteinases (MMPs) are known to play an important role in photoaging by mediating the degradation of extracellular matrix proteins. To develop a new anti-aging agent for cosmetics from natural products, Melothria heterophylla (Lour.) Cogn. was selected for its antioxidant activity and inhibitory effect on expression of MMP-1 in UVA-irradiated human skin fibroblasts. Two compounds (compounds 1 and 2 ) were isolated from an ethyl acetate soluble fraction of the ethanolic extracts; they were identified as 1,2,4,6-tetra-O-galloyl-beta-(D)-glucopyranose (1) and 3,4,5-trihydroxybenzoic acid (2). These compounds were found to scavenge radicals and reactive oxygen species (ROS) and were measured to have SC50 values of 3.9 microM and 13.3 microM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and values of 4.3 microM and 4.0 microM against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Compounds 1 and 2 showed a dose-dependent inhibitory effect on the expression and activity of MMP-1 in UVA-induced human skin fibroblasts, but no inhibition of MMP-1 mRNA expression. Therefore, we concluded that compounds 1 and 2 significantly inhibited MMP-1 expression at the protein level. Also, these compounds were determined to have a potent antioxidant activity. From these results, we suggest that these compounds might be useful as a new anti-aging agent for photodamaged skin, but the in vitro findings must be verified in in vivo studies.

New cosmetic agents for skin whitening from Angelica dahurica.

To develop a new whitening agent for cosmetics from natural products, Angelica dahurica was selected for its inhibitory effect on melanogenesis in B16 melanoma cells. From the mechanism study, it was clarified that the ethanolic extracts of this plant showed the suppression of tyrosinase synthesis but no inhibition of tyrosinase activity. In order to find the active constituents from this plant, the ethanol extracts were chromatographed repeatedly with silica gel. Two coumarin compounds were isolated from A. dahurica. Their structures were identified by physicochemical and spectral data such as UV, IR, NMR, and MS. It was shown that the active substance was isoimperatorin (10-[(3-methyl-2-butenyl)oxy]-7H-furo[3,2-g][1] benzopyran-7-one) and imperatorin (9-[(3-methyl-2-butenyl)oxy]-7H-furo[3,2-g][1] benzopyran-7-one). They significantly inhibited tyrosinase synthesis in B16 melanoma cells. To elucidate the action mechanism of the active compounds of A. dahurica, we investigated the changes in the mRNA level of tyrosinase using the RT-PCR technique. As a result, the mRNA level of tyrosinase was markedly reduced by active compounds of A. dahurica. From these results, we suggest that these extracts might be useful as a new whitening agent in cosmetics, but the in vitro findings must be verified in in vivo skin-lightening studies.

A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxygenase-2.

It has been proposed that Cyclooxygenase (COX)-2 inhibitors may be able to enhance the effects of chemotherapeutic or radiation treatment; however, currently few studies have been reported that define the radiation-enhancing effect of COX-2 inhibitors. We conducted in vitro radiation survival experiments using rat intestinal epithelial cells which were stably transfected with COX-2 cDNA in the sense (RIE-S) and antisense (RIE-AS) orientations to investigate the potential radiosensitizing effect of the selective COX-2 inhibitor, NS-398. Apoptosis was measured using 7-aminoactinomycin-D with flow cytometry to investigate underlying mechanisms for the effect of NS-398 on radiosensitivity. The same experiments were repeated with NCI-H460 human lung cancer cells, which express COX-2 constitutively, and HCT-116 human colon cancer cells, which lack COX-2 expression. In vivo tumor growth delay assays were also performed with tumors formed by H460 and HCT-116 cells. No difference was observed in the intrinsic radiation sensitivity of RIE-S and RIE-AS cells exposed to radiation alone. However, 150-400 microM of NS-398 enhanced radiosensitivity in a concentration-dependent manner in RIE-S cells with dose enhancement ratios of 1.2-1.9 at a surviving fraction of 0.25. However, this effect was not shown in RIE-AS cells. NS-398 enhanced radiosensitivity in H460 cells with a dose enhancement ratio of 1.8 but protected HCT-116 cells from the effects of radiation. Radiation-induced apoptosis was enhanced by NS-398 in RIE-S and H460 cells but not in RIE-AS and HCT-116 cells. Additionally, this radiation-enhancing effect in RIE-S cells seemed to be attributable to some mechanisms other than the reversal of radioresistance induced by COX-2. NS-398 (36 mg/kg) enhanced the effect of radiation on H460 tumors in vivo by an enhancement factor of 2.5; however, it did not enhance the radiosensitivity of HCT-116 tumors (enhancement factor = 1.04). These in vitro and in vivo results suggest that selective COX-2 inhibitors enhance the effect of radiation on tumors that express COX-2 but not on COX-2-lacking tumors. This effect may be attributable to enhancement of radiation-induced apoptosis. Thus, selective COX-2 inhibitors may have potential as radiosensitizers for treatment of human cancers.

Preclinical evaluation of the orally active camptothecin analog, RFS-2000 (9-nitro-20(S)-camptothecin) as a radiation enhancer.

PURPOSE: To test for enhancement of radiation effects in vitro and in vivo by the orally administered camptothecin derivative, 9-nitrocamptothecin (RFS-2000); to study whether the mechanism of this enhancement involves inhibition of sublethal damage recovery. METHODS AND MATERIALS: In vitro: H460 human lung carcinoma cells were incubated with RFS-2000 for various times at 37 degrees C, irradiated, immediately rinsed, and assessed for colony-forming ability. Sublethal damage recovery (SLDR) was also assessed using two split doses of radiation. In vivo: H460 cell xenografts were used in nude mice. Tumors were grown subcutaneously on the flank, then treated with RFS-2000 (1 mg/kg) and/or radiation (2 Gy) for 5 consecutive days. Tumor growth delay was then measured for each treatment group. RESULTS: Radiation enhancement was observed in vitro for incubation times between 4 and 24 hr with 10 nM RFS-2000. Using a 24-hr treatment, the radiation dose enhancement ratio values (DER) for 5, 10, and 15 nM were 1.22, 1.54, and 2.0, respectively. Incubation with 10 nM RFS-2000 inhibited SLDR by a factor of 2. The results of three independent in vivo experiments showed that RFS-2000 can enhance the effects of fractionated radiotherapy, with an enhancement factor (EF) of 1.64. CONCLUSION: Our results show that RFS-2000 can enhance the effects of radiation in human lung cancer cells both in vitro and in vivo, and that the mechanism of this effect may involve the inhibition of SLDR.

The novel taxane analogs, BMS-184476 and BMS-188797, potentiate the effects of radiation therapy in vitro and in vivo against human lung cancer cells.

PURPOSE: To evaluate the novel taxane analogs, BMS-184476 and BMS-188797, as potential radiosensitizers in vitro and in vivo. METHODS AND MATERIALS: Human H460 lung cancer cells were incubated with either paclitaxel or a taxane analog and irradiated at various times. Surviving fractions were then determined using a clonogenic assay. Three different schedules were used: (A) 1-h drug incubation with radiation at t = 8 h, (B) 1-h drug incubation with radiation at t = 24 h, (C) 24-h drug incubation with radiation immediately after. Cell cycle redistribution by taxanes alone was measured with propidium iodide and flow cytometry. Percent apoptosis was also measured using 7-aminoactinomycin D (7-AAD) staining with flow cytometry. For in vivo studies, H460 cell xenografts were used in nude mice. Tumors were grown s.c. on the flank and then treated with BMS-184476 (10 mg/kg i.p. injection, Days 0, 2, and 4) and/or radiation (2 Gy/day, Days 0-4). Tumor growth delay was then measured for each treatment group. RESULTS: The mean in vitro radiation dose enhancement ratios of BMS-184476, BMS-188797, and paclitaxel were 1.76, 1.49, and 1.31 for Schedules A, B, and C, respectively. Isobologram analysis showed that BMS-184476 was synergistic with radiation using Schedule A. Treatment with taxanes caused an increase in the percentage of G2/M cells at the time of irradiation. The mean fold increases in the %G2/M above control values for all three drugs were 5.6, 2.5, and 1.7 for Schedules A, B, and C, respectively. The combined effects of taxanes plus radiation on the induction of apoptosis were additive for all three drugs. In vivo studies showed that BMS-184476 can enhance the effects of fractionated radiotherapy, with an average enhancement factor of 1.66 obtained from three independent experiments. CONCLUSIONS: These results demonstrated that the novel taxane analogs, BMS-184476 and BMS-188797, can enhance the effects of radiation in human lung cancer cells both in vitro and in vivo. These data also support the hypothesis that a G2/M block is involved in the radiosensitization caused by the taxanes.

Phosphorylation of tau at THR212 and SER214 in human neuronal and glial cultures: the role of AKT.

We have reported recently that the microtubule-associated protein tau is phosphorylated in vitro by Akt, an important kinase in anti-apoptotic signaling regulated by insulin and growth factors. We also established that Akt phosphorylates tau separately at T212 and S214, two sites previously shown to be phosphorylated by glycogen synthase kinase 3beta (GSK3beta) and protein kinase A (PKA), respectively. In the present studies, we examined the relationship between Akt and T212/S214 in primary cultures of human neurons and astrocytes, and evaluated the contribution of two other kinases. In intact cells, we found a very low content of active (phospho-S473) form of Akt. We also found a low content of phospho-S214 but not phospho-T212 of tau, suggesting that only phospho-S212 may depend on Akt activity in situ. We upregulated Akt activity using two experimental models: treatment with a protein phosphatase inhibitor, okadaic acid, and transfection with a constitutively active Akt gene construct (c-Akt). Under these conditions, phosphorylation of tau at T212 and S214 was regulated independently, with little change or downregulation of phospho-T212 and dynamic upregulation of phospho-S214. Our studies revealed that Akt may influence the phospho-S214 content in a meaningful manner. They also revealed that PKA may only partially contribute to the phosphorylation of S214. In comparison, okadaic acid treatment severely depleted the content of GSK3beta and downregulated the remaining GSK3beta activity by Akt-dependent inhibition, consistent with minimal changes in phospho-T212. In summary, these results strongly suggest that in primary cultures, Akt selectively phosphorylates tau at S214 rather than T212. Our studies raise the possibility that tau S214 may participate in Akt-mediated anti-apoptotic signaling.

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck.

BACKGROUND AND PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. MATERIAL AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20-70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1-6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. CONCLUSIONS: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.

cAMP potentiates beta-amyloid-induced nitric oxide release from microglia.

The beta-amyloid peptide (Abeta) has been known to activate microglia and to induce release of nitric oxide (NO). In this study, we examined the effect of cAMP on Abeta-induced microglial activation using cultured rat brain microglia. Dibutyryl-cAMP (dbcAMP) and 3-isobutyl-1-methylxanthine (IBMX) significantly potentiated Abeta(25-35)- or Abeta(1-42)-induced NO release in a dose-dependent manner. The increase in NO release was due to the increased expression of inducible nitric oxide synthase (iNOS). However, forskolin, an adenylate cyclase activator, weakly increased NO release at 10-50 microM but caused a decrease at 100 microM. These results suggest that increase in intracellular cAMP could potentiate microglial activation induced by Abeta.

Mitogen-activated protein kinases activated by lipopolysaccharide and beta-amyloid in cultured rat microglia.

To test whether mitogen-activated protein kinases (MAPKs) are involved in microglial activation, pure microglia prepared from 1- to 3-day-old rat brains were activated with either 100 ng/ml lipopolysaccharide (LPS) or 5 nM synthetic beta-amyloid (Abeta) (25-35). The patterns of MAPK activation following LPS and Abeta treatment were very similar. Three MAPK subtypes, p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) were activated within 15 min and the activities of p38 and ERK were rapidly reduced to background level within 30 min while that of JNK was maintained for over 1 h. Both inhibitors of p38 (SB203580) and ERK pathway (PD098059) reduced LPS-induced nitric oxide (NO) release and Abeta-induced tumor necrosis factor-alpha (TNF-alpha) release. Furthermore, co-treatment of SB203580 and PD098059 additively reduced NO and TNF-alpha release. These results suggest that MAPK, at least p38 and ERK, mediate LPS-, and Abeta-induced microglial activation.

Expression and function of outward K+ channels induced by lipopolysaccharide in microglia.

Cultured microglia exposed to lipopolysaccharide (LPS) express outward K+ currents. These currents are due to the expression of new K+ channels detected by antibodies against Kv1.5, a shaker type delayed rectifier. We examined whether the K+ currents are involved in microglial activation. The amount of nitrite, converted from nitric oxide (NO), was measured as an indication of microglial activation [Chao, C. C., Hu, S., Molitor, T. W., Shaskan, E. G., and Peterson, P. K. (1992) J. Immunol. 149, 2730-2741]. Nitrite was detected starting from 24 h after LPS treatment and continuously increased over 4 days. Contrary to this, in the presence of 4-aminopyridine (4-AP, 2 mM), a blocker of outward K+ currents, nitrite production was reduced to less than 50%. However, the treatment of 4-AP 24 h after LPS did not reduce nitrite production. Other K+ channel blockers having a less blocking effect on outward K+ currents, such as 5 mM tetraethylammonium (TEA) and 1 mM Cs+, had little effect. The present study shows that the outward K+ channels induced by LPS are immunologically related to Kv1.5 and also suggests that these channels are required for microglial activation, particularly for the initiation of the activation process.

Combined effects of the orally active cisplatin analog, JM216, and radiation in antitumor therapy.

PURPOSE: We evaluated the orally administered platinum agent, JM216, in combination with ionizing radiation both in vivo and in vitro against human tumor cells. METHODS: H460 human lung carcinoma cells were used as a subcutaneous xenograft in nude mice. JM216 (30 mg/kg) was administered orally, and radiation treatments (2 Gy) were given 1 h after JM216 delivery for five consecutive days. For in vitro analysis, attached H460 cells were treated with JM216 (15 microM) for 1 h and then irradiated. Cells were rinsed 20 min later, and survival was determined by clonogenic assay. RESULTS: Tumor growth delay measurements showed that the combination of JM216 and radiation was additive in vivo, with an enhancement ratio of 1.24. In vitro clonogenic survival experiments demonstrated a dose enhancement ratio of 1.23. Isobologram analysis showed that this interaction was also additive. CONCLUSIONS: These data demonstrate that the combination of JM216 and fractionated radiotherapy is more effective against human lung cancer xenografts than either agent alone, and the in vivo results were supported by those observed using an in vitro system with the same tumor cell line.

Topoisomerase I inhibitors in the combined modality therapy of lung cancer.

Locally advanced non small-cell lung cancer (NSCLC) represents 30%-40% of all pulmonary malignancies. Despite the fact that the disease is confined to the chest, most patients will eventually succumb to their dis-ease. Therefore, the management of NSCLC is undergoing rapid evolution with hope of improving overall survival. The arrival of a new generation of chemotherapeutic agents, including the taxanes, gemcitabine, and topoisomerase inhibitors such as irinotecan and topotecan, offers the hope of real advances against this malignancy. Irinotecan and topotecan are camptothecin derivatives that are felt to exert their cytotoxic effects by targeting topoisomerase I. It is believed that topoisomerase I inhibitors stabilize a DNA-topoisomerase I cleavable complex, and interactions between this complex and the replication machinery may lead to cell death. There is a significant volume of in vitro and in vivo data demonstrating that these topoisomerase I inhibitors also act as radiosensitizers. Early clinical data with topotecan suggests that it is a more active agent in small-cell lung cancer than it is in NSCLC despite a common mechanism of action with irinotecan. With the increasing data that exist on the improved outcome with concurrent chemoradiation treatment for malignancies including lung cancer and head and neck cancers, there is an impetus to pursue the addition of other drugs that can radiosensitize tumors and further improve local control. Irinotecan is undergoing early clinical trials in the combined modality setting in several different disease sites. This paper will review the in vitro and in vivo data on the ability of irinotecan and topotecan to render tumors more susceptible to ionizing radiation. It will then focus on the experience with both drugs and thoracic radiation in the treatment of NSCLC, in which irinotecan has yielded acceptable toxicity results and response rates in excess of 60% in early trials. It is hoped that newer treatment strategies, such as the combination of radiation and topoisomerase I inhibitors in lung cancer, will have a significant impact on cure rates in the future.

Sensitive determination of bisphenol A in environmental water by gas chromatography with nitrogen-phosphorus detection after cyanomethylation.

A new technique is proposed for the determination of bisphenol A in environmental water. The sample preparation consists of a single-step extraction of bisphenol A from a water sample with methylene chloride and the cyanomethyl derivatization of bisphenol A. 2,2'-Biphenol is used as an internal standard. Bisphenol A and biphenol can be quantitatively converted to their corresponding cyanomethyl ethers, which are then measured by gas chromatography with nitrogen-phosphorus detection. Peak shape and quantification of bisphenol A are excellent, with linear calibration curves over a range of 0.1-100 ng/ml. The detection limit is 0.1 ng/ml in water samples. The average recovery and RSD at a concentration of 5 ng/ml are 89.3 and 4.5%, respectively. The procedure is applicable to the quantification of bisphenol A in tap water, raw water and stream water.

Role of taxanes in the combined modality treatment of patients with locally advanced non-small cell lung cancer.

The plant-derived taxanes have a unique mechanism of cytotoxic action and have shown interesting response and survival data in metastatic non-small cell lung cancer (NSCLC). Based on these results, taxane-based regimens have been investigated in combination with radiotherapy in unresectable NSCLC. Trials with paclitaxel-based concurrent chemoradiotherapy have shown 50-100% tumour response rates, 12-26 month median survivals and 32-52% 2-year survival rates. Trials with concurrent chemoradiotherapy with docetaxel have shown 35-92% tumour response rates, 12-23 month median survivals, and 41-43% 2 year survival rates. Taxane-based concurrent chemoradiotherapy for stage III NSCLC appears promising. Large ongoing randomised trials will define the role of these agents in the treatment of locally advanced NSCLC.

Delayed onset of diuresis in a patient with acute renal failure due to hemorrhagic fever with renal syndrome who also developed anterior hypopituitarism.

A 23-year-old man developed acute renal failure (ARF) due to hemorrhagic fever with renal syndrome (HFRS). The patient also developed anterior hypopituitarism as a complication of HFRS. The patient's oliguric phase was very much prolonged for over 10 days before the diuresis began. The urine output during the oliguric phase was near anuric (< 50 ml/day). Interestingly, the patient began to diurese just after the institution of glucocorticoid and thyroid hormone replacement therapy. The plasma atrial natriuretic polypeptide went up to a smaller peak (150.0 pg/ml) at the onset of diuresis compared with 15 other patients (292.4 +/- 190.4 pg/ml) who did not develop anterior hypopituitarism. The delayed onset of diuresis and smaller increase of plasma ANP may have a causal relationship with the patient's hypopituitarism.

Renal biopsy in elderly patients: clinicopathological correlation in 117 Korean patients.

AIM: In the elderly with renal disease, the clinical presentations are frequently inconsistent with the pathologic findings. We tried to clarify the differences in pathological findings between the young and the elderly, in Korea and in Western countries, and the usefulness of a percutaneous renal biopsy in the elderly with renal disease. PATIENTS AND METHODS: We analyzed the clinical presentations and spectrums of renal histopathology by reviewing medical records and renal biopsy reports retrospectively in 117 Korean patients aged 60 years or more with renal disease. RESULTS: 85 patients had primary renal disease. The remaining 32 patients had renal diseases associated with systemic conditions. Out of the 85 patients with primary renal disease, 61 cases presented as idiopathic nephrotic syndrome. Compared with renal biopsy results of younger adult patients (age 15-59, n = 1,908), membranous nephropathy, crescentic glomerulonephritis, membranoproliferative glomerulonephritis, amyloidosis, light chain disease, and thrombotic thrombocytopenic purpura were more prevalent, but IgA nephropathy and lupus nephritis were less common in the elderly patients. In clinical presentation, nephrotic syndrome and rapidly progressive renal failure were more prevalent, but asymptomatic urinary abnormality was less common in elderly patients. The responsiveness to treatment was good in elderly patients with minimal-change lesion (complete remission in all patients) but poor in crescentic glomerulonephritis, IgA nephropathy, and membranoproliferative glomerulonephritis. From the above findings, the clinical presentation, patterns of histopathology and responsiveness to treatment of elderly Korean patients were similar to those of the younger Korean control group and the Western elderly group. CONCLUSION: Percutaneous renal biopsy is a useful diagnostic aid and can be used as a therapeutic guideline even in elderly patients with renal disease.

Neoadjuvant chemotherapy and radiation for inoperable carcinoma of the maxillary antrum: a matched-control study.

A matched-control study comparing standard radiotherapy versus neoadjuvant chemotherapy and radiation was undertaken to clarify the effects of neoadjuvant systemic chemotherapy for locally advanced squamous cell carcinoma of the maxillary antrum. Thirty-four patients with inoperable maxillary cancer were treated with neoadjuvant chemotherapy and radiotherapy (Group II). Before starting radiotherapy, all patients in Group II received two or three cycles of neoadjuvant chemotherapy consisting of cisplatin and a 5-day continuous infusion of 5-fluorouracil with or without intravenous injection of vinblastine. Radiation doses ranged from 66 Gy to 75 Gy (median, 70 Gy). The response rate, patterns of failure, toxicity, and survival for Group II were compared with those for 34 stage-matched patients treated with radiation alone (Group I). Despite a higher response rate to neoadjuvant chemotherapy, the recurrence rate and patterns of treatment failure were not influenced by the addition of neoadjuvant chemotherapy. In most cases, neoadjuvant chemotherapy did not interfere with subsequent radiotherapy, and radiation-induced late complications occurred equally in both treatment groups. After a median follow-up of 48 months, there was no significant difference in 5-year actuarial survival or disease-free survival between the two treatment groups. Radiation alone for inoperable maxillary cancer was clearly suboptimal for improving local control and survival rate, but neoadjuvant chemotherapy in addition to standard radiotherapy failed to demonstrate any therapeutic advantage over radiation alone.