Intraovarian actions of oestrogen.

Oestrogen regulates several hypothalamic and pituitary hormones, which in turn control ovarian functions. Oestrogen and its metabolites, such as catecholoestrogens, also have direct effects within the ovary. This review examines the roles of oestrogen in regulating ovarian folliculogenesis, ovulation and corpus luteum formation. Oestrogen promotes follicular development, which culminates in ovulation, by potentiating follicular development, granulosa cell expression of gonadotrophin receptors, steroidogenesis, and gap junction formation by granulosa cells, and by inhibiting granulosa cell apoptosis. In addition, oestrogen may be needed for corpus luteum formation and maintenance. Studies on mutant mice that either lack one or both of the known oestrogen receptors or are unable to synthesize oestrogen support some but not all of these prior inferences of the roles of oestrogen within the ovary. Although these transgenic mice have proved useful in determining some of the intraovarian actions of oestrogen, they present confounding problems, including hormonal imbalances, that hinder interpretation. Transgenic mice with conditional or tissue-directed mutations in their oestrogen receptors are needed to dissect the ovarian actions of oestrogen further. In addition, microarray technologies, combined with specific hormone treatment regimens are likely to provide an attractive, alternative approach to using mutant mice in clarifying the direct actions of oestrogen in the ovaries of other species.

Detection and discrimination of PrPSc by multi-spectral ultraviolet fluorescence.

Prion diseases are progressive degenerative disorders of the central nervous system. The transmissibility and fatal nature of these diseases necessitate their rapid and accurate diagnosis. The hallmark of these diseases is the accumulation of PrPSc, a protease-resistant form of a host-coded glycoprotein. We have been evaluating the use of multi-spectral ultraviolet fluorescent spectroscopy as a means of detecting and distinguishing between different forms of PrPSc. Spectroscopic measurements of fluorescence from untreated and proteinase K (PK)-treated PrPSc, purified from 263K scrapie strain-infected hamster brains and ME7 scrapie strain-infected mouse brains, were performed. Spectra of untreated and PK-treated PrPSc samples for 263K and ME7 appeared qualitatively different. The identification and discrimination of PrPSc were possible based on these spectral signatures, calculations of their fluorescence cross sections, and determination of the orthogonal differences. This technique has the potential not only for the sensitive, specific, and direct detection of PrPSc, but also for the ability to distinguish between different forms of the prion protein.

Distinguishability of biological material by use of ultraviolet multispectral fluorescence.

Recent interest in the detection and analysis of biological samples by spectroscopic methods has led to questions concerning the degree of distinguishability and biological variability of the UV fluorescent spectra from such complex samples. We show that the degree of distinguishability of such spectra is readily determined numerically. As a practical example of this technique, we show its application to the analysis of UV fluorescence spectra taken of E. coli, S. aureus, and S. typhimurium. The use of this analysis to determine the degree of biological variability and also to verify that measurements are being made in a linear regime in which analytic methods such as multivariate analysis are valid is discussed.

The safety and efficacy of thoracoscopic lung biopsy for diagnosis and treatment in infants and children.

Thoracoscopic techniques were used to perform lung biopsies and limited resections in 36 consecutively treated cases. Biopsies were performed for interstitial lung disease in 27 cases, presumed metastatic lesions in 5, and cavitary lesions in 4. Histological diagnosis was obtained in 35 of the 36 cases, and therapy was directly affected by the results in 30 of 36 cases. There were no postoperative complications, and the average hospital stay for patients admitted the morning of surgery was less than 2 days. Limited thoracoscopic resection provides a safe and effective means for diagnosing and treating parenchymal disease of the lung.

The mangled extremity syndrome (M.E.S.): a severity grading system for multisystem injury of the extremity.

The severely mangled extremity presents a challenge in appropriate surgical management. Very few objective data were found about this problem. To clarify the situation, criteria for a "mangled extremity' were defined, a multidisciplined approach employed, and a retrospective graduated grading system developed. Sixty consecutive trauma patients with severely injured extremities during the past 3 years were reviewed. Seventeen patients fit the category of Mangled Extremity Syndrome (M.E.S.). Injuries were retrospectively classified using a graduated grading system directed at four major tissue systems of the extremity involved (integument, nerve, artery, and bone). Additional scoring items were included to define the significance of trauma sustained outside the extremities. Patients who ultimately came to amputation could have been identified preoperatively at initial emergency evaluation utilizing this graduated grading system. Retrospective data suggest that a Mangled Extremity Syndrome Index (M.E.S.I.) of 20 is the dividing line below which functional limb salvage can be expected and above which limb salvage is improbable. Prospective application of this system, as well as an organized multidisciplined approach, could be useful in the identification of functionally retrievable versus probably irretrievable extremities, thus identifying and helping define the indications for amputation. The grading system criteria and results in these 17 patients form the basis of this report.

Resection of hepatic metastases from colorectal cancer.

We studied 141 patients who had resection of hepatic metastases from colorectal cancer, considering all such lesions removed between 1948 and 1982. The study involved extended observations of patients described previously. Also included were 21 patients who had wedge resections of small metastases done since 1976, who, therefore, did not qualify for analysis of major hepatic resections reported recently (1980 and 1983). The overall five-year survival rate was 25%, significantly higher than that of a group of historical controls who had resectable metastases that were not removed. The size and nature of our extended sample allowed identification of some determinants of favorable prognosis: Dukes' stage of the primary lesion, absence of extrahepatic metastases, and being female. Contrary to our earlier observations, this study justified removal of some multiple hepatic metastases.

The natural history of hepatic metastases from colorectal cancer. A comparison with resective treatment.

Five-year survival after resection of hepatic metastases from colorectal cancer is 25%. Although resection palliates some patients who do not live that long, 50% of patients so treated are not helped at all. Until ignorance of a cancer's real stage is resolved by improved techniques, the evaluation and choice of therapy can be based only upon knowledge of the natural history of untreated metastases and determinants of prognosis derived from treated patients. Analysis of the survival rates of 252 patients who had biopsy proven, unresected hepatic metastases that were the only evidence of residual disease shows the extent to which natural history, rather than resection, may determine length of survival-- and indicates the need for critical analysis of 2- and 3-year survival rates reported after any therapy. Study of 141 patients who had hepatic metastases resected shows that the stage of the primary lesion, being female, and the absence of extrahepatic metastases are significant determinants of favorable prognosis after resection of hepatic metastases.