Sporotrichoid lymphocutaneous infections: etiology, diagnosis and therapy.

Sporotrichoid lymphocutaneous infection is an uncommon syndrome that is often misdiagnosed and improperly treated. Of the several hundred cases seen each year in the United States, the majority are caused by Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum or Leishmania brasiliensis. The "sporotrichoid" disease begins at a site of distal inoculation and leads to the development of nodular lymphangitis. Systemic symptoms are characteristically absent. By recognizing the distinct pattern of nodular lymphangitis and focusing on the diverse but limited etiologies, the physician can obtain the appropriate histologic and microbiologic studies and start targeted antimicrobial therapy. Therapy is generally continued for two to three months after the resolution of cutaneous disease.

Undetected vancomycin-resistant Enterococcus in surgical intensive care unit patients.

The rates of vancomycin-resistant Enterococcus (VRE) in a high-risk population were investigated prospectively using an active surveillance method. The costs of conducting active surveillance were calculated. Among the 10 patients found to have VRE, routine cultures identified 3 (30%); thus, 70% of the VRE-colonized patients would have gone undetected in the absence of active surveillance. The total cost for 5 weeks of active surveillance was $2,234. Although active surveillance identified a high rate of VRE-colonized patients who otherwise may not have been identified, it remains to be determined if the additional costs are justified and result in reduced transmission.

Oculoglandular syndrome. Cat-scratch disease without the cat scratch.

Oculoglandular syndrome and swelling of the parotid gland are unusual manifestations of cat-scratch disease. Although exposure to cats is considered an important part of the patient history, an actual cat scratch is not required to establish the diagnosis. Oral fluoroquinolones show promise in the treatment of the infection.

The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1.

Cells from the human monocytic cell-line THP1 were incubated prior to activation with IFN-gamma or LPS with varying amounts of p24, the main product of the HIV gag gene and the major component of the virus core. The IFN-gamma-dependent increase of mRNA for HLA-DR and for the heavy chain of cytochrome b was markedly decreased by p24 but not by gp120. This effect was abrogated by anti-p24 antibodies. On the other hand, preincubation of THP1 cells with p24 did not affect the accumulation of the LPS-dependent mRNA for TNF alpha and IL1-beta. These results indicate that p24 at concentrations similar to those found in the serum of HIV-infected individuals specifically affects IFN-gamma-induced activation markers.

Immunohistologic and histochemical methods for detection of steroid binding in breast cancer: a reappraisal.

A review of the current literature on immunohistologic and histochemical methods for the detection of steroid hormone binding sites in breast cancer, reveals that many, but not all of the criteria for establishing hormone-receptor binding interactions have been met. These include tissue specificity, binding between labeled ligands and soluble receptor in vitro, correlations between histochemical and biochemical assays, as well as between histologic procedures and tumor hormone responsiveness. However, histochemical binding phenomena do not appear to follow classical receptor dogma in regard to the concentration of ligand required, or specificity of binding as determined by competitive binding assays. It is concluded that these histologic techniques may be detecting classical receptor that may be reacting differently than would be expected from biochemical analyses, Types II and III binding sites, and/or organelle and membrane-bound receptors. Certainly no current method should presently be promoted as a laboratory method for the detection of classical receptor. New immunocytologic procedures employing specific, antireceptor sera currently under development, may obviate many of the criticisms leveled against earlier methods.

Histochemical assay of estrogen and progesterone receptors in breast cancer: correlation with biochemical assays and patients' response to endocrine therapies.

Estrogen (ER) and progesterone (PgR) receptors were assayed by histochemistry in primary, recurrent, and metastatic breast cancer. Ligand-conjugates composed of 17 beta-estradiol and 11 alpha-hydroxyprogesterone covalently linked to bovine serum albumin and labelled with fluorescein isothiocyanate were employed. Results were compared with those of conventional biochemical receptor assays and correlated for ER in 92% of 314 tumors and for PgR in 86% of 86 specimens. ER and PgR determinations by both assay systems were correlated with clinical response to various endocrine therapies in 40 women with Stage IV disease. The histochemical assay enabled successful prediction of response in 80% of cases including eight which could not be fully analyzed biochemically.

Histochemical analyses of steroid hormone receptors in breast and prostatic carcinoma.

Histochemical analyses estrogen (ER) and progesterone (PgR) receptors in breast cancer were statistically correlated with results of dextran-coated charcoal (DDC) and sucrose gradient assays. Correlated for ER was 91% of 363 cases, and for PgR 88% of 255 specimens. Breast cancer ER/PgR positivity by histochemistry correlated with a favorable clinical response to endocrine therapies in 72% of 25 cases, while ER/PgR negativity correlated with a lack of response in 96% of 22 cases with Stage IV disease. Nuclear ER/PgR correlated with a poor response to therapy in 8 of 12 patients. An in vitro technique to detect nuclear translocation of ER revealed two groups of ER positive cases, with 11 of 17 exhibiting translocation and 6 not displaying translocation. In prostatic carcinoma, 72% of 65 men were positive for ER and/or androgen receptor. Comparison of specimens obtained without and with electrocautery revealed a preponderance of nuclear binding in the latter, suggesting heat-induced nuclear translocation of receptor. coumestrol, a naturally fluorescent, entirely unaltered estrogen was also used for histochemical detection of ER. Results correlated with ER by DCC in 87% of 61 breast cancers. Coumestrol was additionally used to visually observe receptor and nuclear translocation of ER in intact whole cells in culture.

The role of progesterone receptors in the management of advanced breast cancer.

The identification of steroid receptors in human breast cancer tissues has provided biochemical markers to predict hormone responsiveness. Analysis of tumors from 328 patients for the estrogen receptor protein (ERP) revealed significant levels in 225 patients (68%). Fifty-five patients with advanced disease were subjected to hormonal manipulation. Thirty patients underwent ablative surgery consisting of adrenalectomy or adrenalectomy and oophorectomy. Twenty-five patients were treated with additive therapy utilizing the new antiestrogen Tamoxifen. The ECOG criteria for an objective response were applied to all patients. Fifteen of the 24 estrogen receptor-positive patients (63%) subjected to endocrine ablation responded. Eleven of twenty (55%) ERP-positive patients responded to Tamoxifen therapy. Only one ERP-negative patient responded in the total group. Simultaneous analysis of these same specimens for the progesterone receptor protein (PgRP) revealed that 151 patients were ERP and PgRP positive (46%); 74 (23%) were ERP positive and PgRP negative; 90 (27%) were ERP and PgRP negative, and 13 (4%) were ERP negative and PgRP positive. In the two treatment groups the overall response rate when both receptors were positive was 77% with a higher percentage of responders in the endocrine ablative group (88% vs. 64%). In addition, a greater duration of response was achieved in those patients treated with endocrine ablation.

Hormone relationships in breast cancer: the role of receptor-binding proteins.

The introduction of receptor protein studies as markers for hormone dependence of breast carcinomas has had a profound effect on the management of advanced disease. All breast carcinomas, regardless of stage, should have receptor binding protein studies for estrogen and progesterone by the sucrose gradient method or by the dextran-coated charcoal method as a good alternative. A simpler test is needed. In cases of primary advanced disease or in recurrent disease, receptor binding protein studies effectively identify the subgroup of hormone-dependent tumors that should be managed by surgical hormone ablation or endocrine manipulation. These tests are even more effective in identifying patients that should not receive hormone therapy and respond better to chemotherapy. In primary, potentially surgically curable disease, receptor studies may serve as a therapeutic guide to adjuvant hormone or chemotherapy. In all breast cancers, ER and PgR receptor studies should be performed and the information should be stored for possible future use. If possible, tisssue should be stored in a freezer in anticipation of future tests and for confirmation of hormone dependence in the event of recurrence.

Histochemistry of steroid receptors in breast cancer: an overview.

Immunofluorescence and a new histochemical technique were employed to assay 226 breast cancer specimens for estrogen receptor. Results showed an overall correlation of 91 percent when compared to those of biochemical assays. The histochemical technique is rapid, easy to perform and reveals the same parameters as does immunofluorescence without the need for antiserum. Tumor cell receptor heterogeneity and location of receptor in cytoplasm or nucleus is readily defined by both methods. These histologic tests should prove to be useful in extending the availability of estrogen receptor analysis to all patients with breast cancer.

A histochemical technique for evaluation of progesterone receptors in breast cancer.

A histochemical method for the detection and localization of progesterone receptors in human breast cancer has been developed employing a fluorescein labeled conjugate of bovine serum albumin linked to a progestin as the binding hormone. Considerable tumor cell receptor heterogeneity was apparent and nuclear binding was frequently noted. The results of the new assay correlated with those obtained by dextran-coated charcoal assay in 91 per cent of specimens.

Immunofluorescent detection of estrogen receptors in breast cancer. Comparison with dextran-coated charcoal and sucrose gradient assays.

Biopsy specimens from 106 women with primary operable, recurrent or metastatic breast cancer were analyzed in a double blind study designed to compare the results of a new fluorescent antibody method for detection of estrogen receptors with estrogen receptors measured biochemically with dextran-coated charcoal and sucrose gradient assay techniques. Assay results correlated in 89.4% of tumors analyzed, and molecular receptor forms (8S and 4S) were accurately predicted in 94.7% of neoplasms studied. Divergent results most often occurred in specimens sparsely populated with malignant cells. The new technique permitted recognition of possible sources of false negative results such as necrosis, absence of tumor and, on occasion, estrogen bound in vivo. It was possible to analyze by the immunofluorescence method two specimens of insufficient size for biochemical assay.

Changes in carbohydrate tolerance during long-term oral contraception.

An intravenous glucose tolerance test (GTT) was given to 116 women--82 nondiabetic subjects (NDS) and 34 diabetes suspects--before they received Ovulen for oral contraception. Subjects were followed for 1 to 4 years during Ovulen therapy. Twenty women using an intrauterine device showed no changes in glucose tolerance. Prompt, significant decline in tolerance was noted in NDS, persisting for the duration of the study. At least one abnormal test, indicating chemical diabetes, was noted in 13 per cent of the NDS. Similarly, prompt decline in tolerance, although not statistically significant, was observed in the suspect group. Fifteen per cent of suspects had at least one abnormal test. Chemical diabetes persisted during Ovulen therapy in suspects but not in NDS. No overt diabetes occurred. Based on greater concern regarding suspects, a procedure for monitoring carbohydrate tolerance is proposed for this group.