Effects of glucocorticoids on declarative memory function in major depression.

BACKGROUND: Major depression has been associated with hypercortisolemia in a subset of patients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects has been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexamethasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). METHODS: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or dexamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. RESULTS: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3. CONCLUSIONS: These findings are consistent with an altered sensitivity of declarative memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethasone-induced reductions in cortisol, in patients with MDD.     

The treatment of donor sites with cultured epithelial grafts

In a significant number of elderly patients, the healing of split skin donor sites can be delayed. The cultured allogenic epithelial graft (CAG) has been reported to heal leg ulcers. The mechanism of action may be to improve the healing environment and thus stimulate the host skin cells. A clinical trial was undertaken to compare the healing rate of the donor sites of elderly patients using CAGs and two commercially available dressings. Compared to Jelonet, CAGs (p = 0.008) and OpSite (p = 0.013) significantly reduced the number of patients with delayed healing. There was no significant difference between CAGs and the occlusive dressing, OpSite.     

The Effect of Cuts in Medicare Reimbursement on Hospital Mortality

Objective. To determine if patients treated at hospitals under different levels of financial strain from the Balanced Budget Act (BBA) of 1997 had differential changes in 30-day mortality, and whether vulnerable patient populations such as the uninsured were disproportionately affected.
Data Source. Hospital discharge data from all general acute care hospitals in Pennsylvania from 1997 to 2001.
Study Design. A multivariate regression analysis was performed retrospectively on 30-day mortality rates, using hospital discharge data, hospital financial data, and death certificate information from Pennsylvania.
Data Collection. We used 370,017 hospital episodes with one of four conditions identified by the Agency for Healthcare Research and Quality as inpatient quality indicators were extracted.
Principal Findings. The average magnitude of Medicare payment reduction on overall net revenues was estimated at 1.8 percent for hospitals with low BBA impact and 3.6 percent for hospitals with a high impact in 1998, worsening to 2 and 4.8 percent, respectively, by 2001. Operating margins decreased significantly over the time period for all hospitals ( p <.05). While unadjusted mortality rates demonstrated a disproportionate rise in mortality for patients from high impact hospitals from 1997 to 2000, adjusted analyses show no consistent, significant difference in the rate of change in mortality between high-impact and low-impact hospitals ( p =.04–.94). Similarly, uninsured patients did not experience greater increases in mortality in high-impact hospitals relative to low-impact hospitals.
Conclusions. An analysis of hospitalizations in the Commonwealth of Pennsylvania did not find an adverse impact of increased financial strain from the BBA on patient mortality either among all patients or among the uninsured.     

Conservatively Treated Breast Cancer: Outcome by Histologic Subtype

Abstract: Between 1970 and 1990, 1,008 patients with early-stage breast cancer were treated by conservative surgery without axillary dissection followed by radiation therapy to the intact breast in the Department of Therapeutic Radiology at Yale-New Haven Hospital. The patient population, broken down by histologic subtype, was as follows: 761 patients presented with infiltrating ductal carcinoma, 70 patients with pure intraductal, 38 intraductal with focal invasion, 54 infiltrating lobular, 21 tubular, 17 medullary, 16 mucinous, and 29 with other various histologic subtypes. Patients were followed on a regular basis by the referring physicians and radiation oncologists. Diagnostic studies for distant metastases were performed as clinically indicated. Annual mammography was a routine component of the follow-up program. As of 3/96, with a median follow-up of 10.5 years, 83 patients developed an ipsilateral breast tumor recurrence, and 109 patients developed distant metastases resulting in an overall 10-year breast recurrence-free rate of 84%, and a 10-year distant metastasis-free rate of 78%. There were significant differences in clinical stage, pathological nodal involvement, and administration of systemic therapy between various histologic subtypes. As expected, those patients with histologies of low metastatic potential (such as intraductal, tubular, and mucinous) had significantly superior distant recurrence-free survival rates. With respect to breast relapse rates, there were no statistically significant differences in the 5- and 10-year breast recurrence-free rates between any of the histologic subtypes. Patients with intraductal carcinoma with or without focal invasion had similar breast relapse rates as those with other histologic subtypes. Patients with lobular carcinoma in situ as a histologic component also had a similar overall breast relapse-free recurrence rate. In conclusion, long-term follow-up of conservatively treated breast cancer patients demonstrates no significant differences in ipsilateral breast tumor recurrence rates between various histologic subtypes. There are no histologies which had a statistically significantly higher breast-relapse rate than infiltrating ductal carcinomas and therefore no primary histologic subtype represents a relative contraindication to breast conservation therapy.     

A survey of general surgeons' attitudes towards breast reconstruction after mastectomy.

Within the last 15-20 years there have been many changes in the management of breast cancer. Along with changes in treatment, possibilities for breast reconstruction have become increasingly sophisticated and commonplace. Despite the availability of breast reconstruction, we have noted large variations in referral patterns. Because the surgical treatment of breast cancer is largely undertaken by general surgeons, we investigated general surgeons' attitudes towards reconstruction using a postal questionnaire. In 1995, a questionnaire involving hypothetical criticisms was sent to general surgical members of the Association of Surgeons of Great Britain and Ireland. A total of 136 surgeons responded, 79 (58%) of whom had a specialist interest in breast cancer. Each surgeon saw an average of 68 new cases of breast cancer per year (range 0-400). The general surgeons were concerned about three areas: (1) 32.3% felt that breast reconstruction might adversely delay the detection of local recurrence; (2) 16.6% were worried that breast reconstruction has high morbidity; and (3) 17.4% said that patients did not want breast reconstruction despite being advised of its availability. To investigate these concern's further, an extensive literature search was undertaken. There is no evidence that breast reconstruction delays the detection of local recurrence. With appropriate patient selection, the morbidity of reconstructive options appears very acceptable. Finally, immediate breast reconstruction has psychological benefits when compared with delayed reconstruction.     

Efficacy of chemopreventive agents for growth inhibition of Apc [+/-] 1638NCOL colonic epithelial cells

Germline mutations of the Apc tumor suppressor gene result in increased risk for gastrointestinal carcinogenesis. The Apc1638N [+/-] mouse exhibits accelerated gastrointestinal carcinogenesis that is modifiable by select pharmacological and dietary agents. Experiments in the present study were conducted on a subculturable epithelial 1638NCOL cell line established from histologically normal colon of Apc1638N [+/-] mouse to examine the effects of selected chemopreventive agents that differ in their mechanism of action. Extent of growth arrest, number of cell population doublings, cell cycle progression and aneuploid G0/G1: S + G2/M ratio represented the quantitative endpoints for the susceptibility and efficacy of chemopreventive agents. Treatment of exponentially growing 1638NCOL cells with maximum cytostatic dose of 9cisRA, DFMO or SUL (100 microM) produced a 60-70% growth arrest, that with TAM and AMF (10 microM) produced a 20-40% growth arrest, while that with OLT (100 microM) produced a 25% growth arrest. This response was associated with corresponding decrease in the number of cell population doubling. 9cisRA, SUL or AMF increased the aneuploid G0/G1: S + G2/M ratio by inducing G1 checkpoint arrest, while DFMO, TAM and OLT decreased the ratio by inducing G2 checkpoint arrest. Thus, cell cycle phase-dependent susceptibility of the Apc [+/-] 1638NCOL cell line to mechanistically distinct chemopreventive agents validates a novel colon epithelial cell culture model for mechanistic, preventive or therapeutic studies on Apc regulated colon carcinogenesis.     

Diffuse neuroendocrine differentiation in a morphologically composite mammary infiltrating ductal carcinoma: a case report and review of the literature

Neuroendocrine differentiation has been reported in both in situ and infiltrating breast cancers. The prognostic significance of neuroendocrine differentiation in mammary carcinoma is unclear. We report a case of infiltrating ductal carcinoma in which there was a morphologically conventional-appearing infiltrating ductal component admixed with nests of cells that resembled a carcinoid tumor and initially mimicked the appearance of intraductal carcinoma. Immunohistochemical stains for synaptophysin and chromogranin demonstrated diffuse, strong positivity uniformly throughout the tumor, even in the more conventional-appearing areas. Electron microscopic examination of tissue retrieved from paraffin blocks was attempted unsuccessfully. We concluded that this was an infiltrating ductal carcinoma with morphologic and immunohistochemical evidence of neuroendocrine differentiation. The case is discussed with a review of the literature and a discussion of nomenclature for tumors of the breast showing variable degrees of neuroendocrine differentiation.