Comparison of the Humphrey swedish interactive thresholding algorithm (SITA) and full threshold strategies

PURPOSE: To compare the Swedish interactive thresholding algorithm (SITA) strategy with the full threshold strategy in routine clinical practice. METHODS: Using the Humphrey visual field analyzer model 750 (Allergan Humphrey, San Leandro, CA), 108 subjects were tested with 24-2 SITA (version A9) and 24-2 full threshold strategies. Test results were compared for time taken and reliability and on the basis of seven criteria of abnormality. RESULTS: The SITA required on average 48.8% less time than the full threshold strategy. Patient reliability parameters were somewhat better with SITA. There was a strong correlation between mean deviation and pattern standard deviation. Average threshold sensitivity at each point was increased by 1.31 dB with SITA, but greater differences were seen at points with lower sensitivity. Using the full threshold strategy as our standard for comparison, the sensitivity of SITA varied from 83.0% to 93.2% in detecting the variously defined abnormalities. Fields shown as normal with full threshold strategy corresponded with those found to be normal with SITA in 79.0 to 96.3% cases depending on criteria for abnormality. There were a few cases in which SITA suggested an early abnormality but results of full threshold testing remained normal. On average, the size and depth of scotomas decreased slightly with SITA, but this difference was not statistically significant. Of the 70 patients surveyed about their preference, 65 (92.9%) preferred SITA. CONCLUSION: Full threshold and SITA strategies are comparable in detecting glaucomatous defects. The SITA strategy requires significantly less time to perform and is a satisfactory alternative to full threshold algorithms in clinical practice for diagnosis and management of glaucoma.     

A late complication of spousal kidney donation

An 83-year-old female who had previously (32 years ago) donated a kidney to her husband presented with loin pain, confusion and oliguria. Acute renal failure and pulmonary edema necessitated emergency hemodialysis. The history and findings were thought to be consistent with acute renal artery occlusion on a background of atherosclerosis and severe renal artery stenosis. We present this case, not to imply that renal donation is a hazardous procedure, but rather as an illustration of a complication of donor nephrectomy that in a very large series has proved to be extremely rare. This case illustrates the point that even very rare events become more likely as the period of follow-up increases.     

A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions

The best current model of breast cancer evolution suggests that most cancers arise from certain premalignant lesions. We have identified a common (34%) somatic mutation in the estrogen receptor (ER)-alpha gene in a series of 59 typical hyperplasias, a type of early premalignant breast lesion. The mutation, which affects the border of the hinge and hormone binding domains of ER-alpha, showed increased sensitivity to estrogen as compared with wild-type ER-alpha in stably transfected breast cancer cells, including markedly increased proliferation at subphysiological levels of estrogen. The mutated ER-alpha exhibits enhanced binding to the TIF-2 coactivator at low levels of hormone, which may partially explain its increased estrogen responsiveness. These data suggest that this mutation may promote or accelerate the development of cancer from premalignant breast lesions.     

Mid-Systolic closure of the aortic valve in hypertrophic obstructive cardiomyopathy: A pressure-Related phenomenon induced by turbulent blood flow

The purpose of this study was to determine whether mid-systolic closure and opening of the aortic valve in patients with hypertrophic obstructive cardiomyopathy (HOCM) may reflect dynamic changes of pressure induced by turbulent blood flow in the aorta and left ventricular outflow tract. Five patients with HOCM who had echocardiographic evidence of mid-systolic closure of the aortic valve and two patients with HOCM who did not have transient mid-systolic closure of the aortic valve were studied. In patients in whom mid-systolic closure was present, a transient mid-systolic drop of pressure was present in the left ventricular outflow tract, distal to the dynamic intraventricular obstruction, 17 ± 3 mm Hg (mean ± SEM) and in the root of the aorta, 16 ± 4 mm Hg. In these patients the mid-systolic drop of pressure was consistently associated with a high-intensity intracardiac murmur indicative of turbulence. In the two patients in whom mid-systolic closure of the aortic valve was absent, the transient mid-systolic drop of pressure during systole was minimal (average, 3 mm Hg). The transient mid-systolic drop of pressure distal to the intraventricular obstruction can be explained on the basis of decreased pressure energy of the blood due to turbulence. Since total energy is conserved, increased kinetic energy due to turbulence occurs at the expense of a loss in pressure energy. The transient mid-systolic reduction of pressure in the turbulent zone during systole may cause a pressure differential across the open valvular leaflets resulting in a transient closure of the aortic valve.     

Estrogen receptor positivity in mammary tumors of Wnt-1 transgenic mice is influenced by collaborating oncogenic mutations

The majority (75%) of human breast cancers express estrogen receptor (ER). Although ER-positive tumors usually respond to antiestrogen therapies, 30% of them do not. It is not known what controls the ER status of breast cancers or their responsiveness to antihormone interventions. In this report, we document that transgenic (TG) expression of Wnt-1 in mice induces ER-positive tumors. Loss of Pten or gain of Ras mutations during the evolution of tumors in Wnt-1 TG mice has no effect on the expression of ER, but overexpression of Neu or loss of p53 leads to ER-negative tumors. Thus, our results provide compelling evidence that expression of ER in breast cancer may be influenced by specific genetic changes that promote cancer progression. These findings constitute a first step to explore the molecular mechanisms leading to ER-positive or ER-negative mammary tumors. In addition, we find that ER-positive tumors arising in Wnt-1 TG mice are refractory to both ovariectomy and the ER antagonist tamoxifen, but lose ER expression with tamoxifen, suggesting that antiestrogen selects for ER-negative tumor cells and that the ER-positive cell fraction is dispensable for growth of these tumors. This is a first report of a mouse model of antiestrogen-resistant ER-positive breast cancers, and could provide a powerful tool to study the molecular mechanisms that control antiestrogen resistance.     

Comparative uptakes and biodistributions of internalizing vs. noninternalizing copper-64 radioimmunoconjugates in cell and animal models of colon cancer

Copper-64-labeled monoclonal antibodies (mAbs) have previously demonstrated unexpectedly effective tumor control in rodent models of cancer at relatively low tumor-absorbed radiation doses. This property has been associated with delivery platforms resulting in cellular internalization. The purpose of the present studies was to evaluate the in vitro internalization and in vivo distribution of a two-antibody model of ⁶⁴Cu radioimmunotherapy (RIT) in the same cell and animal models of cancer. Biodistributions of an internalizing antibody, cBR96, and a noninternalizing antibody, cT84.66, labeled with ⁶⁴Cu, were obtained in nude mice bearing LS174T colon carcinoma xenografts from 15 min to 48 h. The ⁶⁴Cu-DOTA-cBR96 conjugate demonstrated rapid tumor uptake, reaching 20.2% ID/g at 3 h and peaking at 35.4% ID/g by 24 h. Tumor accumulation of ⁶⁴Cu-DOTA-cT84.66 was more gradual, 8.19% ID/g at 3 h and 43.8% ID/g by 24 h, but maximum uptake was not statistically different from ⁶⁴Cu-DOTA-cBR96. Mouse xenograft dosimetry was estimated to be 1128 rad/mCi (304.9 mGy/MBq) for ⁶⁴Cu-DOTA-cBR96 and 1409 rad/mCi (380.5 mGy/MBq) for ⁶⁴Cu-DOTA-cT84.66. In LS174T cells, internalized radioactivity increased by a factor of 3.8 over 4 h for ⁶⁴Cu-DOTA-cBR96, but remained unchanged ⁶⁴Cu-DOTA-cT84.66. When normalized to uptake at 1 h, cellular efflux of ⁶⁴Cu was essentially identical for both mAbs. The biodistributions and tumor dosimetry of these internalizing and noninternalizing radiolabeled mAbs were sufficiently similar for direct comparison of the therapeutic efficacies of low doses of ⁶⁴Cu RIT agents in the same animal model of cancer.     

Complete regression of visceral Kaposi's sarcoma after conversion to sirolimus

The prevalence of Kaposi's sarcoma (KS) is much greater in organ transplant recipients than it is in the general population. Its etiology appears to be related to geographic, genetic, and viral factors. Treatment of transplant-related KS has, until now, consisted mainly of reduction of, or withholding of, immunosuppression, often with deleterious effects on both graft and patient survival. In recent years, the immunosuppressive drug, sirolimus, has been demonstrated as possessing anti-neoplastic properties in both in vitro and animal models. In view of these properties and some preliminary clinical experience, we postulated that sirolimus would be beneficial in our patients who developed transplant-related KS. Here, we report the first case of a patient with both cutaneous and visceral KS who was successfully treated in the Middle East by conversion from a cyclosporine-based to a sirolimus-based immunosuppression regimen. The KS regressed completely within a few months after the conversion. The chronologic events and the extensive documentation, which included repeat computed tomography scans, are very suggestive of a selective anti-neoplastic effect of sirolimus.     

Maspin expression in invasive breast cancer: association with other prognostic factors

Maspin is a unique serine protease inhibitor with a molecular weight of 42 kDa. It has been shown to inhibit tumour cell motility and invasion in cell culture, and tumour growth and metastasis in animal models. There is very limited data on the prognostic utility of maspin in human breast cancer. We performed a preliminary study to assess the associations of maspin with other established prognostic factors in invasive breast cancer (IBC). 1068 paraffin-embedded IBCs were immunohistochemically stained with a monoclonal antibody to maspin. A nuclear signal was present in 96% and a cytoplasmic signal in 35% of the cases. Nuclear staining was related to oestrogen (ER) and progesterone receptor (PR) positivity (p < 0.0001), but not to S-phase fraction (SPF) or ploidy. Cytoplasmic staining was related to ER and PR negativity (p < 0.0001), high SPF (p < 0.0001), and aneuploidy (p = 0.003). Thus, maspin nuclear staining was significantly associated with good prognostic factors, while cytoplasmic staining was associated with poor prognostic markers. These findings suggest that the presence of maspin in two different compartments of the cell may have different biological and clinical implications. Additional studies are needed to evaluate further this expression profile of maspin in breast cancer.