Primary phacoemulsification and aspiration combined with 25-gauge single-port vitrectomy for management of acute angle closure.

PURPOSE: To describe a technique using phacoemulsification and aspiration (PEA) combined with 25-gauge single-port vitrectomy as a primary treatment for acute angle closure (AAC). METHODS: Seventeen consecutive cases of AAC were treated with 1) transconjunctival limited single-port vitrectomy with a 25-gauge vitrector and 2) transcorneal PEA and cortex removal followed by implantation of foldable intraocular lenses (IOL). RESULTS: Intraocular pressure (IOP) control was achieved in all 17 eyes examined. Mean preoperative IOP was 51.8+/-13.1 mmHg, and mean IOP on postoperative day 1 was 18.3+/-8.5 mmHg. Additional anti-glaucoma surgery was necessary in one eye. IOL could not be implanted because of zonular dialysis in one eye. Postoperative complications were seen in three cases (one retinal hemorrhage and two papilledema). CONCLUSIONS: The PEA procedure is efficient as a primary treatment of AAC. Single-port vitrectomy with a 25-gauge vitrector facilitated PEA and IOL implantation.

Chorioretinal temperature monitoring during transpupillary thermotherapy for choroidal neovascularisation.

AIMS: To investigate the difference in temperature rise between normal choroid and choroidal revascularisation (CNV) during transpupillary thermotherapy (TTT) and the relation between laser spot size and power in the rat fundus. METHODS: A modified slit lamp, which was installed with two laser wavelengths (490 nm for illumination and fluorescein excitation and 810 nm for hyperthermia), was developed for TTT and temperature monitoring. Temperature rise during TTT was monitored by observing fluorescence released from thermosensitive liposomes encapsulating carboxyfluorescein. Two types of liposomes were prepared; their phase transition temperatures were 40 degrees C and 46 degrees C, respectively. Laser power settings required to observe fluorescence released from 46 degrees C liposome in normal choroid or CNV were compared. Next, the power settings with 0.5 mm and 0.25 mm spot sizes were compared following administration of 40 degrees C liposome or 46 degrees C liposome. RESULTS: The minimum power values when release from 46 degrees C liposome was observed showed a significant difference in distribution of power values between normal choroid and CNV. CNV required significantly higher power than normal choroid. With 40 degrees C liposome, the power was 9.7 (1.9) mW (mean (SD)) at a spot size of 0.25 mm, and 12.1 (1.6) mW at 0.5 mm, respectively. When using 46 degrees C liposome, the power setting was 10.2 (1.2) mW at a spot size of 0.25 mm, and 14.6 (2.2) mW at 0.5 mm, respectively. CONCLUSIONS: CNV demonstrated varying heat conduction, compared with normal choroid. Laser power required to raise the temperature should not necessarily be doubled, even when the spot size is doubled. Close attention should be given to the selection of power settings when performing TTT for CNV.

Pars plana vitrectomy for cystoid macular edema secondary to sarcoid uveitis.

OBJECTIVE: To examine the results of pars plana vitrectomy for cystoid macular edema secondary to sarcoid uveitis resistant to medical treatment. DESIGN: Retrospective, interventional, noncomparative case series. SUBJECTS: Fourteen consecutive subjects (18 eyes) with cystoid macular edema associated with sarcoid uveitis resistant to medical treatment. INTERVENTION: All eyes underwent pars plana vitrectomy. Nine eyes also underwent peeling of the epiretinal membrane or removal of the posterior vitreous cortex. MAIN OUTCOME MEASURES: Status of macular edema, visual acuity, and complications. RESULTS: Ten eyes (56%) improved 2 or more lines of Snellen visual acuity within 12 months. Six eyes (33%) remained unchanged, within a line of preoperative Snellen visual acuity, and two eyes (11%) worsened by 2 or more lines of Snellen visual acuity. Slit-lamp biomicroscopy showed that cystoid macular edema had resolved in 14 eyes (78%) within 9 months postoperatively. One eye (6%) had minimal edema, whereas three eyes (17%) remained unchanged biomicroscopically at the final visit. Postoperative complications included cataract formation, glaucoma, optic nerve atrophy, epiretinal membrane formation, and tractional retinal detachment. No severe postoperative inflammation was noted. CONCLUSIONS: Pars plana vitrectomy seems to have a beneficial effect on cystoid macular edema caused by sarcoidosis resistant to medical treatment.

Therapy-related leukemia and myelodysplasia following oral administration of etoposide for recurrent breast cancer.

We report a high risk of therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) in patients receiving oral administration of etoposide for recurrent breast cancer. We examined 119 patients with recurrent disease. Patients were initially treated with anthracyclines, cyclophosphamide, or cisplatin with or without radiation before etoposide treatment. Etoposide was used as the final drug in most cases. Twenty-four patients were treated with the oral administration of etoposide (50 or 100 mg/day for 5-7 days at 4-week intervals). Three cases of t-AML/MDS developed among those 24 patients exposed to etoposide. In contrast, the development of t-AML/MDS was not observed in the other 95 patients not treated with etoposide. Our data suggest that there is a substantial risk of secondary leukemia with oral administration of etoposide for a prolonged period as well as i.v. schedules.

Simultaneously found transient hypothyroidism due to Hashimoto's thyroiditis, autoimmune hepatitis and isolated ACTH deficiency after cessation of glucocorticoid administration.

We present a 42-year-old woman with concomitant transient hypothyroidism due to Hashimoto's thyroiditis, autoimmune hepatitis and isolated ACTH deficiency. Two months after ceasing prednisolone (5 mg/day) for uveitis, she was discovered incidentally to have liver dysfunction with hypergammaglobulinemia, later diagnosed as autoimmune hepatitis by histological examination of the biopsied liver. In addition, primary hypothyroidism due to Hashimoto's thyroiditis and secondary hypocortisolism due to isolated ACTH deficiency were revealed by endocrinological examination. Although not treated, her liver dysfunction and hypothyroid state recovered simultaneously, and the isolated ACTH deficiency was restored six months later. We concluded, after a needle-biopsy of the thyroid, that the transient hypothyroidism was due to Hashimoto's thyroiditis and the reversible ACTH deficiency was probably due to autoimmune hypophysitis. This case shows that cessation of steroid treatment may transiently exacerbate the polyglandular autoimmune syndrome.

Effect of interferon-beta on thyroid function in patients of chronic hepatitis C without preexisting autoimmune thyroid disease.

The effect of interferon-beta (IFN-beta) on thyroid function was studied in patients with chronic hepatitis who had no preexisting thyroid disease. Eleven patients (9 males and 2 females) aged 20 to 65 years, with a mean age of 47.7 +/- 13.5 years, were treated with 6 million units of IFN-beta intravenously every day for 8 weeks. During IFN-beta administration (4th to 8th week of treatment), both serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations decreased significantly (P < 0.0005 and P < 0.05, respectively): FT4, 1.37 +/- 0.17 to 1.09 +/- 0.12 ng/dl, and FT3, 3.71 +/- 0.45 to 3.28 +/- 0.34 pg/ml. On the other hand, serum TSH increased significantly from a baseline of 1.70 +/- 0.82 to 3.34 +/- 1.98 microU/ml during IFN-beta administration (P < 0.005). Four to eight weeks after cessation of treatment, the mean serum FT4 concentration was similar to that during IFN-beta administration (1.04 +/- 0.14 ng/dl), but mean serum FT3 and TSH concentrations returned to pre-treatment levels (FT3, 3.57 +/- 0.42 pg/ml and TSH, 1.60 +/- 0.84 microU/ml). Both reverse T3 and thyroglobulin were essentially unchanged. Tests for anti-thyroglobulin and anti-microsomal antibodies were negative in all the patients. These results indicate that IFN-beta may inhibit thyroid function in patients without preexisting thyroid disease irrespective of humoral immune responses.

Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer.

As part of our evaluation of members of the transmembrane 4 super-family as possible prognostic predictors, we performed a retrospective study on the expression of the recently identified KAI1 gene by tumors of the lung. This gene, which is identical to CD82, suppresses tumor metastasis of prostate cancer, and its decreased expression may be involved in malignant progression. We used reverse transcription-PCR to analyze tumor tissues from 151 lung cancer patients; 74 tumors were stage I, 17 were stage II, and 60 were stage III. Our results indicate that while 35 patients had tumors in which the KAI1/CD82 gene was conserved (positive), 116 patients had tumors with reduced gene expression (negative). The overall survival rate of patients with KAI1/CD82-positive tumors was significantly higher than that of patients with KAI1/CD82-negative tumors (77.4% versus 38.5%; P=0.002). Furthermore, the overall survival rate of patients with KAI1/CD82-positive adenocarcinoma was also much higher than that of individuals whose adenocarcinoma had reduced KAI1/CD82 expression (73.4% versus 27.1%;P=0.009). Multivariate analysis with the Cox regression model indicated that KAII/CD82 positivity correlated best with the overall survival rate, except for lymph node status. Our data suggest that high KAII/CD82 gene expression by tumors of the lung may be associated with a good prognosis. These findings complement our earlier studies on MRP-1/CD9, another member of the transmembrane 4 superfamily, whose reduced expression in non-small cell lung cancer appears to be a factor of poor prognosis. This set of observations suggests that assessment of the expression status of KAI1/CD82 and MRP-1/CD9 by tumors may provide prognostic information on the clinical behavior of lung cancer.

Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer.

Motility related protein-1 (MRP-1) is a transmembrane glycoprotein that is identical to the CD9 antigen. In previous studies, we showed that various types of cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and diminished metastatic potential to the lung. More recently we used immunohistochemical procedures, immunoblotting, and reverse transcription-PCR to demonstrate that the level of MRP-1/CD9 expression was inversely related to the clinical stage of a given carcinoma of the breast. In addition, we found that the primary tumors of almost 50% of the patients had higher MRP-1/CD9 levels than their respective metastatic lymph nodes. In consideration of these findings, we have now applied reverse transcription-PCR to determine MRP-1/CD9 gene expression in lung cancer. We analyzed tumor tissues of 109 patients: 49 tumors were stage I; 15 were stage II; and 45 were stage III. We found that 67 patients had MRP-1/CD9-positive tumors, and that gene expression was reduced in the tumors of the remaining 42 individuals. The overall rate of survival was strikingly higher among patients with positive tumors than in those whose tumors had reduced gene expression (62.3 versus 34.9%; P < 0.001). This also pertained to patients with adenocarcinomas of the lung (55.4 versus 26.0%; P < 0.001). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positivity correlated better with overall survival rate than did other variables, except lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative lung cancer patients and patients with adenocarcinomas who are at high risk for early disease recurrence.

Motility related protein 1 (MRP-1/CD9) expression: inverse correlation with metastases in breast cancer.

In our previous studies we showed that motility related protein 1 (MRP-1) is a glycoprotein recognized by mAb M31-15, and that the sequence of MRP-1 is identical to that of CD9, a WBC differentiation antigen. Transfection of MRP-1/CD9 cDNA into cultured nonhematopoietic cells suppresses cell motility. The extent of suppression is directly related to the level of MRP-1/CD9 expression. In addition, the metastatic potential of MRP-1/CD9-transfected melanoma BL6 cells is lower than that of control BL6 cells. To determine whether these experimental results are of relevance with respect to actual human tumors, we investigated MRP-1/CD9 expression in 143 invasive ductal carcinomas of the breast. Of 97 patients with MRP-1/CD9-positive tumors, only 36 (37.1%) had lymph node involvement. In contrast, 21 of 39 (53.8%) patients whose tumors had reduced MRP-1/CD9 immunoreactivity and 5 of 7 patients whose primary carcinomas were not stained by the anti-MRP-1/CD9 MAb had lymph node metastases. The comparison of protein expression by 62 primary tumors and their respective metastatic lymph nodes revealed that in almost 50% of the cases, the latter had lower MRP-1/CD9 levels than the former. Moreover, reverse transcriptase-PCR-based analysis disclosed that MRP-1/CD9 gene expression in the metastatic lymph nodes of 17 of 32 patients was strikingly lower than in the primary invasive ductal carcinomas. Gene overexpression was not observed in any of the samples studied. Our data suggest that low MRP-1/CD9 expression may be associated with the metastatic potential of certain human tumors.

Cyclosporine A inhibits the secretion of certain anterior pituitary hormones in patients with nephrotic syndrome.

To clarify the effects of cyclosporine A (CsA) on the secretion of serum thyrotropin (TSH), prolactin (PRL), luteinizing hormone (LH) and follicular stimulating hormone (FSH), we performed TRH and LH-RH testing in 4 patients with the nephrotic syndrome before and after the administration of CsA, 6 mg/kg/day for 4 to 12 weeks. Prior to CsA all patients responded normally to TRH with respect to TSH and PRL secretion. Two patients showed normal response of LH and FSH to LH-RH stimulation while the response in 2 other patients, who were both menopausal, was exaggerated. By the third or fourth week of CsA administration the basal and peak TSH and PRL values declined significantly in all patients in response to TRH stimulation while those of LH and FSH showed only a modest decrease in response to LH-RH stimulation. Two to 4 weeks after the cessation of CsA the response of TSH, PRL and FSH returned to the pretreatment level. These observations suggest that: 1) CsA exerts an inhibitory effect on the secretion of at least TSH and PRL in humans, and 2) the effect of CsA on the pituitary may be partially reversible after the cessation of the therapy.

Exacerbation of hypothyroidism following tumor necrosis factor-alpha infusion.

A 46-year-old woman with chronic thyroiditis who had been receiving thyroid hormone treatment for 10 yr developed severe hypothyroidism (FT4 0.37 ng/dl, FT3 1.38 pg/ml, TSH 151.00 microU/ml) following tumor necrosis factor-alpha (TNF) infusion for the treatment of a complicated cutaneous T-cell lymphoma. Indirect immunofluorescence staining of thyroid follicular cells showed aberrant expression of HLA class II antigens. The mechanisms underlying the exacerbation of the hypothyroidism may be an augmentation of immunological processes in the thyroid and a direct action of TNF on the synthesis and secretion of thyroid hormone.

[The frequency and mechanisms of urolithiasis in acromegaly].

It is generally accepted that acromegaly is often associated with hypercalciuria, but there are few reports on the frequency and the mechanisms of urolithiasis. Recently we consecutively experienced 2 cases of acromegaly with urolithiasis, and these experiences made us investigate the association between urolithiasis and acromegaly. Among 18 acromegalies from 1977 to March 1990 (10 males, 8 females, 24-64 years old), 13 cases (72%) fulfilled the criteria of hypercalciuria (urinary calcium (u-Ca) greater than or equal to 200 mg/day or u-Ca/urinary creatinine (u-Ca/u-Cr) greater than or equal to 0.15), and 7 cases (39%) suffered from urolithiasis that was diagnosed by KUB (4 cases) or X-ray computed tomography (CT) (3 cases). Especially in the last 2 years, 5 out of 7 cases (71%) were complicated with urolithiasis and all 7 cases were associated with hypercalciuria. These results suggest that hypercalciuria and urolithiasis are both much more frequent than previously reported. In 6 cases who were treated by pituitary adenomectomy from 1988-1989 (4 males, 2 females, 24-59 years old), we examined Ca metabolism before and after operation. Before operation, the levels of serum growth hormone (GH), u-Ca (mg/day), u-Ca/u-Cr (in all cases) and plasma somatomedin-C (Sm-C) (in 4 cases) were increased above the normal range. To determine the etiology of hypercalciuria, we performed the oral Ca load test under restriction of Ca (400 mg/day) and P (650 mg/day) intake. The results suggested that the hypercalciuria might be mainly due to the increased absorption of Ca from the intestine (so-called "Absorptive hypercalciuria"). However, the levels of serum vitamin D (Vit. D) metabolites were all within the normal range before operation. After operation, GH and u-Ca/u-Cr (in 5 cases) and u-Ca (mg/day) (in all cases) decreased significantly compared with before operation, and the levels of Sm-C (in all cases), serum 25-(OH)D3, 1 alpha, 25-(OH)2D3 (in 4 cases) and 24,25-(OH)2D3 (in 3 cases) were also reduced after operation. Surprisingly, u-Ca and u-Ca/u-Cr normalized only in 4 cases who showed a reduction in 1 alpha, 25-(OH)2D3 levels after operation, although there were no correlations between u-Ca (mg/day) or u-Ca/u-Cr and 1 alpha, 25-(OH)2D3. Significant correlations were found between u-Ca (mg/day) or u-Ca/u-Cr and Sm-C. The parathyroid function evaluated by the rapid Ca infusion test or nephrogenous cyclic adenosine monophosphate (NcAMP) was normal before and after operation.(ABSTRACT TRUNCATED AT 400 WORDS)

Cyclosporine A (CyA)-induced decrease of serum gonadotropin levels in a case of Klinefelter's syndrome.

We report a case of Klinefelter's syndrome who developed a decrease of serum gonadotropin levels, particularly LH, after CyA treatment for complicated focal glomerulosclerosis (FGS). A 38-year-old man suffering from general malaise and pretibial edema was diagnosed FGS by renal biopsy in October 1988, and was referred to our hospital for further evaluation and treatment for FGS in December 1988. He was not married, and closer anamnesis revealed that he had had impaired seminal ejaculation from the age of 30. The physical examination showed 37% obesity, scanty body hair, pretibial edema and small bilateral testes (3.0 x 1.5cm). Laboratory findings included marked proteinuria (5.3g/day) and mild renal dysfunction (serum creatinine 1.3mg/dl, glomerular filtration rate 57.2ml/min). Endocrinologically, high basal levels of LH and FSH (133.6mIU/ml and 93.7mIU/ml, respectively) and the hyperresponses of LH and FSH to LH-RH stimulation were found, but the other pituitary hormone levels, thyroid and adrenal status, were in the normal range. In testicular biopsy, nodularly proliferated Leydig cells and no seminal tubules could be seen. The chromosome analysis showed 47,XXY karyotype, which confirmed the diagnosis of Klinefelter's syndrome in this patient. From 9 January 1989, CyA (6mg/Kg.day) was orally administered for 4 weeks in order to treat for FGS. After CyA administration, basal levels of LH and FSH remarkably decreased, particularly LH, and their decrease lasted for at least 6 weeks after cessation of CyA (final levels; LH 28.2mIU/ml, FSH 69.8mIU/ml). On the other hand, serum testosterone level was low normal or slightly under normal, and no apparent changes could be seen during CyA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)