Phase I study of irinotecan and gefitinib in patients with gefitinib treatment failure for non-small cell lung cancer.

BACKGROUND: Currently, no effective treatments exist for non-small cell lung cancer (NSCLC) after failure of gefitinib therapy. Pre-clinical studies have demonstrated that gefitinib-resistant NSCLC cells are more sensitive to irinotecan than parental cells, and that combined administration of irinotecan and gefitinib has a synergistic additive effect. We conducted a phase I study to evaluate the combination of irinotecan and gefitinib as a therapeutic option for NSCLC patients with progressive disease (PD) after initial gefitinib treatment. METHODS: Eligibility criteria included histologically confirmed NSCLC, age range of 20-74 years, refractory to or relapsed after gefitinib treatment, one or more previous chemotherapy regimens, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and informed consent. Patients were treated with irinotecan on days 1 and 15, and treated daily with gefitinib from day 2 every 4 weeks. The treatment was continued until disease progression. The gefitinib dose was fixed at 250 mg. Irinotecan dosing started at 50 mg m(-2) and was escalated in patients by 25 mg m(-2) increments up to a maximum dose of 150 mg m(-2). RESULTS: Twenty-seven patients were enrolled: male/female=14/13; median age=60 (45-75); histology, adenocarcinoma/non-adenocarcinoma=25/2; performance status 0-1/2=19/8; previous response to gefitinib, partial response/stable disease/PD=21/2/4. Dose-limiting toxicities were observed in 2 patients at level 3. Maximum tolerated dose was not determined, and the full dose of irinotecan could be combined with the full dose of gefitinib. The disease control rate (DCR) and response rate (RR) were 69.2 and 26.9%, respectively. For 12 patients at level 5 (the recommended phase II dose), the DCR and RR were 75.0% and 41.7%, respectively. The median treatment cycles were 4; median time to treatment failure, 57 days (95% confidence interval (CI), 32-82 days); median overall survival, 244 days (95% CI, 185-303 days); and 1-year survival rate, 32.6%. CONCLUSION: The combination of irinotecan and gefitinib was well tolerated and potentially beneficial for NSCLC patients failing initial gefitinib monotherapy.

Lactobacillus rhamnosus alleviates intestinal barrier dysfunction in part by increasing expression of zonula occludens-1 and myosin light-chain kinase in vivo.

The effects of lactobacilli on impaired intestinal barrier function and paracellular permeability were evaluated in human epithelial Caco-2 cells treated with tumor necrosis factor-alpha and in mice with colitis induced by dextran sodium sulfate (DSS). Filter-grown Caco-2 monolayers were used as the intestinal epithelial model. Among the 4 lactobacilli studied, Lactobacillus rhamnosus OLL2838 most effectively suppressed barrier impairment and increased IL-8 secretion induced by tumor necrosis factor-alpha in Caco-2 cells; however, the conditioned medium from OLL2838 did not show any effect on barrier functions. The in vivo effects of OLL2838 on intestinal epithelial barrier function and colonic inflammation were assessed in DSS-induced colitis of BALB/c mice. Oral treatment with both live and heat-killed OLL2838 suppressed weight loss and recovered colon length. Additionally, barrier function was restored by the administration of live and heat-killed OLL2838 to the DSS-treated animals, which conferred protection against the increase in mucosal permeability associated with DSS-induced colitis. This may at least partially be because of the increased expression of zonula occludens-1 (4.8-fold) and myosin light-chain kinase (3.1-fold) in intestinal epithelial cells isolated from mice of the heat-killed OLL2838 group. Therefore, L. rhamnosus OLL2838 would be useful in the treatment of gastrointestinal diseases such as inflammatory bowel disease.

Cell wall fraction of Enterococcus hirae ameliorates TNF-alpha-induced barrier impairment in the human epithelial tight junction.

AIMS: The evaluation of the effects of Enterococcus hirae, an intestinal bacterium in the adjacent mucosa (mucosal bacterium), on tumour necrosis factor-alpha (TNF-alpha)-induced barrier impairment in human epithelial Caco-2 cells. METHODS AND RESULTS: The filter-grown Caco-2 monolayers were used as an intestinal epithelial model system. In Caco-2 cells, heat-killed E. hirae ATCC 9790(T) suppressed the TNF-alpha-induced barrier impairment and increase in interleukin-8 (IL-8) secretion, but lipase- and mutanolysin-treated E. hirae ATCC 9790(T) did not have these effects. It was demonstrated that lipoteichoic acid (LTA) from E. hirae ATCC 9790(T) is responsible for Caco-2 cells' recovery from TNF-alpha-induced impairments. In addition, Caco-2 cells had the same response to Toll-like receptor 2 (TLR2) ligand, Pam(3)Cys-Ser-(Lys)(4) as they did to LTA. Increased expression of zonula occludens-1 was observed by the addition of E. hirae ATCC 9790(T) to TNF-alpha-treated Caco-2 cells, and decreased expression of myosin light chain kinase was observed by the addition of LTA and Pam(3)Cys-Ser-(Lys)(4); this, in turn, led to barrier enforcement. CONCLUSIONS: Enterococcus hirae ATCC 9790(T) cell wall fractions, such as LTA, protect against intestinal impairment by regulation of epithelial tight junction via TLR2 signalling. SIGNIFICANCE AND IMPACT OF THE STUDY: Enterococcus hirae could be useful in the treatment of inflammatory bowel disease, as well as other intestinal disorders.

Noninvasive detection of endothelial dysfunction in elderly with NIDDM by ultrasonography.

We compared endothelial function noninvasively in 15 elderly patients with noninsulin-dependent diabetes mellitus (NIDDM) with 12 nondiabetic elderly patients. Using high resolution ultrasound, we measured flow-mediated dilatation (FMD) of the brachial artery and sublingual nitroglycerin (NTG)-mediated dilatation. FMD was significantly impaired in subjects with NIDDM compared with control subjects. In NIDDM subjects, FMD with complications was lower than in subjects with noncomplications. However, there was no significant difference in NTG between NIDDM subjects and the control group. Hyperemic blood flow change was lower in NIDDM subjects, but not significant. These results suggest that elderly patients with NIDDM have impaired L-arginine/nitric oxide (NO) pathways and the possibility of capillary rarefaction.

[Clinical effect of arotinolol hydrochloride and its influence on renal function in elderly patients with essential hypertension].

Arotinolol hydrochloride with alpha-and beta-receptor blocking action, developed in Japan, is mainly used for the treatment of hypertension. The study population consisted of 42 outpatients with essential hypertension with a blood pressure greater or equal to 160/96 mmHg. 10 men and 32 women, with a mean age of 77.5 year. The patients received 10 mg arotinolol hydrochloride daily for 24 weeks which was taken orally twice a day. We evaluated the changes of blood pressure, heart rate and chief complaints of patients before and every 4 weeks during treatment and the renal function before, 12 weeks after and 24 weeks after, the administration of arotinolol hydrochloride. Blood pressure and heart rate decreased significantly after 4 weeks of treatment with arotinolol hydrochloride (p < 0.05). However, no significant changes were found in blood urea nitrogen, serum creatinine, serum albumin, beta2-microglobuline, NAG or creatinine clearance during the 24 weeks of treatment. These results indicate that arotinolol hydrochloride has antihypertensive effects without renal dysfunction in elderly patients with essential hypertension.

[An elderly patient with an insulinoma who had prolonged dementia-like symptoms].

A 77-year-old woman had suffered from memory disturbance and disorientation for two years before she was admitted to the hospital because of confusion. Her score on the Hasegawa dementia scale revised (HDS-R) was 12 points at the time of the first medical examination. No other abnormalities could be found except for a blood glucose concentration of 34 mg/ dl. A Magnetic Resonance Image (MRI) of the brain showed some small lacunae on both sides in the frontal white matter and basal ganglia. After hospitalization, glucose was administered and the blood glucose concentration increased, but the dementia-like symptoms did not resolve. She was discharged because the symptoms were too difficult to control in the general hospital. Although dementia-like symptoms were present even after discharge, they did not necessarily appear during fasting. Six months later she was rehospitalized. The insulin-blood sugar ratio was at least 0.3 and abdominal echogram showed a 1-cm tumor at the tail of pancreas. The pancreas tail was removed and the tumor cells were reacted with anti-insulin-antibodies. One month after the operation, the dementia-like symptoms had resolved. The HDS-R score was improved to 27 points (normal range) 40 days after the operation. The amount of the slow waves in the electroencephalogram decreased 5 months after the operation. The dementia-like symptoms observed in this case could be regarded as the Durchgangssyndrom of Wieck. This syndrome is observed transiently at the time of recovery of deterioration of disturbances of consciousness. But it is treatable. This patient was an interesting case that showed Durchgangssyndrom mimiking dementia associated with insulinoma.

Urinary angiotensin-converting enzyme activity in type 2 diabetes mellitus: its relationship to diabetic nephropathy.

Urinary angiotensin-converting enzyme (ACE) and urinary N-acetyl-beta-D-glucosaminidase (NAG) were measured after a 5-year interval in 38 non-azotemic type 2 diabetic patients. Of these patients at baseline, 16 had nil nephropathy, 15 had incipient nephropathy, and 7 had overt nephropathy. During the follow-up, 6 and 1 of the 16 patients with nil nephropathy developed incipient and overt nephropathy, respectively. Four of the 15 patients with incipient nephropathy progressed to overt nephropathy. The 7 patients with overt nephropathy continued to have overt nephropathy, with slight azotemia in one. Urinary ACE and NAG levels were normal at baseline and showed no significant elevations at follow-up in the patients with nil nephropathy, no significant changes in baseline and modest elevations at follow-up in the patients with incipient nephropathy, and high at baseline and marked elevations at follow-up in the patients with overt nephropathy. In all patients, urinary ACE during the follow-up was positively correlated with urinary albumin or NAG, but not with glomerular filtration rate. Urinary ACE may be of poor prognostic value for the follow-up of diabetic patients, which is at variance with urinary albumin.

Rhabdomyolysis accompanying thyroid crisis: an autopsy case report.

Rhabdomyolysis is occasionally associated with metabolic disorders such as diabetic coma, severe electrolyte disturbances and myxedema coma. We describe rhabdomyolysis accompanying thyroid crisis. A 50-year-old man with Graves' disease developed rhabdomyolysis, congestive heart failure and hepatic failure during the course of thyroid crisis and then died of acute renal failure. Postmortem examination revealed rhabdomyolysis in the cardiac and psoas muscles, old myocardial infarction, hepatic centrilobular necrosis, renal cortical necrosis, and follicular hyperplasia in the thyroid. Circulatory collapse and dehydration under excessive hypermetabolic state presumably suppressed the source of energy and oxygen for muscle cells, leading to cellular damage.

Dependence on pH of permeability towards electrolyte ions of poly(L-lysine-alt-terephthalic acid) microcapsule membranes.

Permeation of electrolyte ions through poly(L-lysine-alt-terephthalic acid) microcapsule membranes was studied as a function of the pH of the medium at different ionic strengths. When the pH of the medium was varied, the permeation rate for 5-sulphosalicylate anions, as well as phenyltrimethylammonium cations, was slow at pH values lower than 4, showed a sudden and large increase in the pH range between 4 and 6, and thereafter remained unchanged. This remarkable change in the permeation rate was found to be produced by an abrupt increase in the microcapsule size observed in the same pH range. Increase in the ionic strength of the medium at pH values higher than 6 increased the rate of anion permeation but decreased the rate of cation permeation due to increase in the screening effect of salt ions on the negative charges in the microcapsule membranes.

[HLA-antigens in thyrotoxic patients with overt diabetes mellitus].

The incidence of thyrotoxicosis accompanied by overt diabetes has been reported to be 2 to 3%. Several workers have suggested the possible role of immunological and inherited factors in the occurrence of thyrotoxic patients with overt diabetes. We investigated, therefore, the clinical characteristics, backgrounds, and HLA antigens in thyrotoxic patients with overt diabetes. In nine thyrotoxic patients with overt diabetes (group DM) (3 men and 6 females, average age of 45.8 +/- 2.9 yr), mean levels of free-triiodothyronine (FT3) and free thyroxine (FT4) were 8.2 +/- 0.8 pg/ml and 4.9 +/- 0.4 ng/dl, respectively. Although these levels were extremely high, they were significantly lower than those levels in forty thyrotoxic patients without overt diabetes (group ND) (8 men and 32 females, average age 35.1 +/- 4.5 yr). Mean levels of both thyrotrophin receptor-antibody (TR-Ab) and thyroid simulating antibody (TS-Ab) in group DM were relatively lower than those in group ND. Mean titers of both antithyroid antibody (TGHA) and antimicrosomal antibody (MCHA) in group DM were also relatively lower than those in group ND, respectively. Regarding the clinical features in thyrotoxic patients with overt diabetes, mean duration of diabetes mellitus was 4.1 +/- 2.5 years with mean levels of fasting plasma glucose (FPG), HbA1c, and serum fructosamine 208.1 +/- 34.0 mg/dl, 10.6 +/- 0.6%, and 3.9 +/- 0.9 mmol/L, respectively. Seven patients in group DM frequently had ketosis or ketoacidosis in their histories, and they had been treated with insulin injection. However, the diabetic complications in group DM were moderate or severe.(ABSTRACT TRUNCATED AT 250 WORDS)

[Erythrocyte sorbitol levels in patients with thyrotoxicosis].

Hyperglycemia and impaired glucose tolerance are frequently observed in patients with hyperthyroidism. However, little is known about whether altered polyol metabolism in hyperthyroidism is present or not. To examine changes in polyol metabolism in hyperthyroidism, we investigated changes in erythrocyte sorbitol, glyceraldehyde reductase (GAR) and sorbitol dehydrogenase (SDH) activities during hyperthyroid and euthyroid states in patients with thyrotoxicosis. Mean levels of erythrocyte sorbitol and GAR were 32.0 +/- 1.6nM/g.Hb and 147.1 +/- 0.3mU/g.Hb, respectively. In thyrotoxic patients in a hyperthyroid state, these values were significantly higher than those in euthyroid controls. Mean level of erythrocyte SDH in thyrotoxic patients was weak but was significantly increased in comparison with that of euthyroid controls. However, mean levels of erythrocyte sorbitol and GAR were remarkably reduced to 23.6 +/- 1.4nM/g.Hb and 125.3 +/- 4.6mU/g.Hb in thyrotoxic patients in a euthyroid state after treatment with anti-thyroid drugs or by subtotal thyroidectomy. Mean level of SDH, on the other hand, was increased after the treatment. In addition, positive correlations were observed between the level of erythrocyte sorbitol or GAR, and the level of free thyroxine(FT4) or free triiodothyronine(FT3). A negative correlation was observed between the level of erythrocyte SDH and the level of FT4 or FT3. These results suggest that the level of erythrocyte sorbitol may be increased through direct acceleration of erythrocyte GAR activity by increased thyroid hormone levels in patients with thyrotoxicosis.

[Changes in TSH-receptor antibody (TR-AB) and thyroid stimulating antibody (TS-AB) after thyroidectomy in thyrotoxic patients].

Changes in TSH-receptor antibody (TR-Ab) and thyroid stimulating antibody (TS-Ab) after thyroidectomy were examined in seventeen thyrotoxic patients (3 males and 14 females, 40.0 +/- 3.4 yr) with positive TR-Ab and TS-Ab. They were subjected to thyroid surgery because of suspected malignancy, methymazol induced agranulocytosis, cardiac failure, recurrent gastric ulcer or emotional instability. Of these patients, 3 were totally thyroidectomized, 11 were subtotally thyroidectomized and 3 were unilaterally lobectomized. Histological findings in these patients showed diffuse hyperplasia in 8 cases, an adenomatous goiter in 3, diffuse hyperplasia plus follicular adenomas in 5, and Hashitoxicosis in one. Their thyroid function before surgery was as follows: T3 level, 3.9 +/- 0.7 ng/ml; T4, 19.5 +/- 3.3 micrograms/dl; free T3, 11.9 +/- 1.2 pg/ml; free T4, 4.9 +/- 1.0 ng/dl; and TSH, 0.9 +/- 0.1 microU/ml. Mean levels of TR-Ab and TS-Ab before surgery were 56.8 +/- 4.6% and 1,218.6 +/- 262.4%, respectively. Positive anti-thyroid antibody (TGHA) was 47.0%, positive anti-microsomal antibody (MCHA) was 88.2% in these thyrotoxic patients, and mean levels of TGHA and MCHA were 1,688 +/- 715 and 89,280 +/- 34,717 times, respectively. After the operation, these parameters were decreased and their thyroid functions became an euthyroid or a hypothyroid state one month later. The incidence of post-operative hypothyroidism was 45.5% in subtotally thyroidectomized patients, 33.3% in unilaterally lobectomized patients and 100% in totally thyroidectomized patients. TR-Ab levels decreased from 56.2 +/- 6.5% before surgery to 24.5 +/- 12.2% 12 months after surgery, but increased again to 35.0 +/- 15.7% 24 months after surgery in subtotally thyroidectomized patients. These levels also decreased from 50.4 +/- 11.0% before surgery to 37.8 +/- 11.4% 12 months after surgery, and remained unchanged to 38.2 +/- 10.4% 24 months after surgery in unilaterally lobectomized patients. On the other hand, in totally thyroidectomized patients, TR-Ab levels decreased and normalized 12 months after surgery. One of subtotally thyroidectomized or unilaterally lobectomized patients developed recurrent thyrotoxicosis with an increased positive TR-Ab. Mean levels of TS-Ab decreased to 28.3 +/- 181.3% and 152.5 +/- 47.9% 12 and 24 months after surgery, respectively, in subtotally thyroidectomized patients. These levels decreased 12 months after surgery and then increased again to 303.6 +/- 130.6% in unilaterally lobectomized patients. On the other hand, TS-Ab levels decreased and normalized to 94.3 +/- 3.9% 6 months after surgery in totally thyroidectomized patients.(ABSTRACT TRUNCATED AT 400 WORDS)

[The effect of angiotensin I converting enzyme inhibitor (SQ 14225) on plasma 18-hydroxycorticosterone and aldosterone in sodium depleted conscious rats].

Altered sodium intake is known to cause a greater change in plasma 18-hydroxycorticosterone (18-OHB) level than in plasma aldosterone level, resulting in an increase of plasma 18-OHB/aldosterone ratio in sodium-depleted man and rats. To evaluate the role of endogenous angiotensin II in the high plasma 18-OHB/aldosterone ratio in sodium-depleted rats, we examined the effect of the angiotensin I converting enzyme inhibitor SQ 14225 on plasma 18-OHB and aldosterone in sodium-depleted (SD) and sodium-repleted (SR) conscious rats. Plasma renin activity (PRA) and plasma angiotensin II were higher in the SD rats than in the SR rats. The ingestion of SQ 14225 caused an increase in PRA and a decrease in plasma angiotensin II, whereas these changes were more prominent in the SD rats than in the SR rats. Plasma 18-OHB and aldosterone levels were higher in the SD rats than in the SR rats. The plasma 18-OHB/aldosterone ratio was also higher in the SD rats than in the SR rats. The ingestion of SQ 14225 caused decreases in plasma 18-OHB and aldosterone levels in both the SR and SD rats, whereas the SQ 14225-induced decreases in plasma 18-OHB and aldosterone levels were more prominent in the SD rats than in the SR rats. Thus, the ingestion of SQ 14225 induced a decrease in the plasma 18-OHB/aldosterone ratio in both the SR and SD rats. The decrease in plasma 18-OHB/aldosterone ratio was more prominent in the SD rats than in the SR rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary excretion of angiotensin-converting enzyme in NIDDM patients with nephropathy.

Twenty-four-hour urinary excretion of angiotensin-converting enzyme (ACE) was investigated in relation to that of albumin and beta 2-microglobulin (beta 2M) in 25 non-insulin-dependent diabetes mellitus (NIDDM) patients without nephropathy, 13 NIDDM patients with incipient nephropathy, 18 NIDDM patients with overt nephropathy, and 14 nondiabetic subjects. NIDDM patients without nephropathy and nondiabetic subjects were similar in albumin, beta 2M, and ACE excretion. NIDDM patients with incipient nephropathy had elevated albumin excretion (P less than .01) and similar beta 2M and ACE excretion compared with nondiabetic subjects. On the other hand, NIDDM patients with overt nephropathy had elevated albumin, beta 2M, and ACE excretion compared with nondiabetic subjects (P less than .01). In all NIDDM patients studied, a positive correlation was found between ACE excretion and albumin excretion (r = 0.76, P less than .001) or beta 2M excretion (r = 0.52, P less than .01). These data suggest that elevated ACE excretion in NIDDM patients with overt nephropathy may be reflective of renal tubular damage.

[A case of chemical hyperthyroidism induced by antiarrhythmic agent amiodarone].

Amiodarone, an antiarrhythmic agent, is known to occasionally induce alterations in thyroid function because of its iodine content and ability to inhibit T4 5'-monodeiodination. We herein describe the drug-induced chemical hyperthyroidism in a diabetic patient with ventricular premature beats. A 46-year-old man with well controlled diabetes mellitus revealed neck swelling during a 4 months' treatment with amiodarone for his frequent occurrence of ventricular premature beats. Physical findings were unremarkable other than grade III diffuse struma. Routine laboratory studies were almost normal. The results of thyroid function studies showed hyperthyroidism, including increases in T4 and free T4, slight increases in T3 and free T3, a marked increase in reverse T3 and a decrease in 123I 24-h uptake. TSH was low and did not respond to TRH. Antithyroid antibodies and TSH receptor antibodies were negative. The findings of the thyroid biopsy were unremarkable except for a mild follicular hyperplasia. After cessation of the drug, T3 and free T3 were returned to normal within 2 weeks, T4 and free T4 within 2 months and reverse T3 after 6 months. These data suggest that the struma and chemical hyperthyroidism observed in our patient were induced by amiodarone treatment.

High-performance liquid chromatographic separation of corticosteroids in plasma of rats. Its application to the determination of the circadian rhythm of 18-hydroxycorticosterone related to aldosterone and corticosterone.

An efficient separation of corticosteroids in plasma of rats was obtained by reversed-phase high-performance liquid chromatography (HPLC). Plasma corticosteroid assays with HPLC separation were used to determine the circadian rhythm of 18-hydroxycorticosterone (18-OHB) and its possible relationship to aldosterone or corticosterone in conscious rats under standard conditions (regular diet; 12-hour light and 12-hour dark cycle). Significant circadian rhythms of plasma corticosterone, 18-OHB and aldosterone were observed with peak values at 20.00 h and nadir values at 08.00 h. The mean ratio of plasma 18-OHB to aldosterone during 24 h was 2.4. The circadian rhythm of 18-OHB was also correlated with that of plasma aldosterone or corticosterone.

Measuring fiber connection loss using steady-state power distribution: a method.

This paper describes conditions for the reproducible measurement of optical fiber connection losses. The steady-state power distribution is characterized by the width of the far-field pattern (FFP). A method is proposed to determine the power distribution in the fiber from the measured FFP. Using this method, connection losses of graded-index fibers are calculated for various widths of the FFP. Calculated results are verified experimentally. The width of the FFP must be controlled to within an accuracy of 3% for a 0.05-dB reproducibility of the connection loss. Connection loss dependence on mismatch of fiber parameters is also calculated. Calculation shows that variations in core radius, numerical aperture, and index gradient have to be controlled to within 3%, 6%, and 0.3, respectively, for the same reproducibility.

Compact wavelength multiplexer using optical-fiber pieces.

The optical-wavelength-division multiplexer reported here is composed of three multimode fiber pieces with dielectric multilayers evaporated on the ends of the fibers, which have been polished obliquely or squarely. The working faces of these fibers are bonded together in a crossed V groove to duplex two wavelengths (lambda = 0.82 and 1.2 microm). The far ends of the joined fiber pieces are left intact for splicing with fiber cables or are terminated with connector ferrules for connection. The multiplexer is small (1 cm square) and lightweight (1.5-3 g). It also shows low insertion loss (1 dB) and cross-talk level (below -40 dB). We have estimated that the cost of this type of component can be reduced to I order of magnitude lower than that of conventional lens and mirror types.

Determination of modal power distribution in graded-index optical waveguides from near-field patterns and its application to differential mode attenuation measurement.

A technique is introduced that determines power distribution in fibers from the measured near-field pattern, assuming that: (1) the optical power distributes uniformly among degenerated modes with the same propagation constant, (2) enough modes are excited to ensure the validity of calculation by geometrical optics, and (3) the phase of each propagation mode has no correlation. Experiments verifed that the fibers have the function of flattening power distribution among modes with the same propagation constant. This fact shows that assumption (1) does not severely limit the applicability of the technique. Wave optical calculation is done to determine the numbers of modes that must be excited to satisfy assumption (2). As an example of application of the technique, differential mode attenuation of graded-index fibers is determined from longitudinal variation of the measured near-field pattern.