Comminuted pelvic fracture with retroperitoneal bleed in a geriatric patient: a case study.

The case study presented involved an 87-year-old Hispanic man who was transferred to the emergency department (ED) of an acute care hospital. The patient was complaining of left hip pain and hitting his head. The patient had fallen backward upon standing from a wheelchair, lost his balance, and suffered an occipital laceration with hematoma. There was a brief loss of consciousness after hitting his head. An external pelvic stabilizer was placed on the patient's pelvis in an attempt to stabilize the comminuted pelvic fractures. Because of the patient's comorbidities and unstable condition, the consulting physician specialists determined that the patient was not a surgical or interventional candidate. Self-tamponed of retroperitoneal bleeding occurred without intervention of angiogram with embolization or laparotomy. A decision was made among the patient, the patient's stepchildren, and the attending physicians for a do-not-resuscitate order. The patient was then transferred to a palliative care unit outside the hospital. This case discusses the physiological changes in geriatric patients and the management of geriatric patients with pelvic trauma and retroperitoneal bleeding.

Measurement of chemopreventive efficacy in skin biopsies.

OBJECTIVE: To explore methods suitable for quantitative assessment of the efficacy of chemopreventive intervention. STUDY DESIGN: High-resolution imagery of nuclei from the suprabasal and basal cell layers of sun-damaged skin were recorded. There were 10 cases. A shave biopsy was taken from an area of clearly evident solar keratosis before and after treatment with 2-difluoromethyl-dlornithine (DFMO) and from the colateral forearm, treated with a placebo. A number of karyometric variables were computed and combined to derive marker features that provided a numeric measure of the degree of nuclear deviation from normal. RESULTS: DFMO treatment was effective overall in reducing the degree of nuclear abnormality seen in the biopsies; in 8 of the 10 cases there was a significant improvement. The placebo-treated arm did not show a statistically different abnormality from the untreated arm. CONCLUSION: Karyometric analysis can provide numeric measures that allow documentation of statistically significant regression of actinic keratotic lesions following treatment with DFMO.

Quantitative study of ductal breast cancer progression: signatures of nuclei in proliferating breast lesions and in situ cancer.

AIMS: The objective of this study is to derive highly specific nuclear signatures (NS's) for the characterization of nuclei of ductal breast epithelium in proliferative lesions and in situ cancers in order to evaluate if nuclear structural changes are able to describe the main events of ductal cancer progression and if the method can be used for objective grading. METHODS: A total of 82 different features descriptive of the nuclear chromatin patterns were computed in nuclei from normal glandular breast tissue, florid hyperplasia, and ductal carcinoma in situ (DCIS) and of DCIS with microinfiltration. The feature values were arranged to form a profile or signature. Measures of difference to a standard profile derived from normal glandular breast tissue were defined. One may then compute a standardized distance measure for a nucleus from "normal". Lesions can be characterized in the same manner, on the basis of the mean profile for all of their nuclei, and on the basis of the distribution of distances of their constituent nuclei from normal. RESULTS: The selected histopathologic patterns on which the diagnostic categories for DCIS are based were found to have corresponding distinctive patterns in the chromatin of the lesion's nuclei. A monotonic trend of ductal neoplastic progression was found. In addition, lesions histologically assessed as belonging to the same diagnostic category were found to offer substantially different distribution patterns. CONCLUSIONS: The full utilization of nuclear texture features allows the derivation of highly specific signatures for nuclei so that a reproducible grading can be performed for prognostic purposes.

Immunohistochemical expression of pi class glutathione S-transferase in the basal cell layer of benign prostate tissue following chronic treatment with finasteride.

BACKGROUND: Glutathione S-transferases (GST) may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Treatment directed at the induction or preservation of GST-pi expression in normal epithelium could have a profound impact on the prevention of prostate neoplasia. Finasteride, a 5-alpha-reductase inhibitor, is used as a chemopreventive agent because it blocks the conversion of testosterone to its byproduct which promotes prostate tumour growth. OBJECTIVE: To investigate GST-pi expression immunohistochemically in benign prostate tissue from untreated patients and from patients chronically treated with finasteride. MATERIALS: Immunostaining with anti-GST-pi antibody was performed on 10 (cysto-) prostatectomy, eight simple prostatectomy, and three transurethral prostatectomy specimens. The first set of 10 prostates was from untreated patients operated on for bladder cancer. The other cases were from patients with benign prostatic hyperplasia and chronically treated with finasteride. None of the specimens in either group showed prostatic cancer, prostatic intraepithelial neoplasia, urothelial carcinoma, or chronic prostatitis. Specimens were evaluated for the presence, intensity, and distribution of immunostaining. RESULTS: Diffuse cytoplasmic immunostaining was observed in the basal cell layer of the untreated specimens. Some variability in the expression of GST-pi was seen within each zone and also between the prostate zones. Only a minority of the secretory cells was stained weakly, mainly in the subnuclear region of the cells facing an uninterrupted basal cell layer. Staining was more homogeneously diffuse in the cytoplasm of the luminal cells facing the basement membrane directly. In the benign epithelium of the finasteride treated specimens the circumferential staining of the basal cells appeared to be more continuous than in the untreated cases, the gaps in the stained basal cell layer being fewer, shorter, or even absent in some ducts and acini. There was no variability in the intensity of staining of the basal cell layer, all the cells being intensely stained in a uniform way. The intensity of staining of the secretory cells was not influenced by finasteride treatment. CONCLUSIONS: Following chronic treatment with finasteride the immunohistochemical expression of pi class glutathione S-transferase in the benign prostate ducts and acini is upregulated in relation to an expanded basal cell layer. This could indicate that finasteride acts as a GST-pi inducer.

Chromatin texture in high grade prostatic intraepithelial neoplasia and early invasive carcinoma.

OBJECTIVE: To evaluate individual nuclei from high grade prostatic intraepithelial neoplasia (PIN) lesions with early invasive carcinoma foci in the area of microinvasion and in the gland in which the microinvasion originated. STUDY DESIGN: High-resolution, digitized images of nuclei from defined locations were recorded and segmented, and karyometric variables were computed. These included a set of 93 features, which form a nuclear signature characterizing the spatial and statistical distribution of the nuclear chromatin. Nuclei in the glandular epithelium were recorded sequentially, along the basal cell layer, at increasing distances from the point of microinvasion and by random selection in the region of microinvasion. RESULTS: At a distance > 60 nuclear locations from the point of microinvasion, the nuclear signatures corresponded to those seen in high grade PIN. Between 40 and 20 nuclear locations removed from the microinvasion focus the signatures began to change gradually until at a distance of 15-5 locations they strongly resembled the signatures seen in adenocarcinoma. The total optical density decreased to values seen in adenocarcinoma, and the nuclear chromatin had finer granularity. While nuclei in high grade PIN followed a widely dispersed total optical density distribution suggestive of wide-ranging aneuploidy, the nuclei in the region of microinvasion exhibited a less dispersed and bimodal total optical density distribution. CONCLUSION: The chromatin texture signatures showed a clear trend: there was an obvious attenuation as the measured nuclei approached the microinvasion area. The decrease in total optical density at the microinvasion might suggest the emergence of one or two clones that can be responsible for the invasive phenotype.

Tissue architecture analysis in prostate cancer and its precursors: An innovative approach to computerized histometry.

AIMS: It is the aim of these studies to derive a numerically defined progression index for prostatic intraepithelial neoplasia (PIN) lesions. METHODS: Histometric and karyometric features were automatically extracted from images of histopathologic sections by a machine vision system. RESULTS: Both histometric and karyometric measures lend themselves to the defining of a progression index. Karyometric features were found to be more sensitive. They allow the detection of very early change. CONCLUSIONS: It is possible to measure progression of PIN lesions with precision. The methodology would lend itself for measurement of regression due to chemopreventive intervention.

Statistical histometry of the basal cell/secretory cell bilayer in prostatic intraepithelial neoplasia.

OBJECTIVE: To delineate the sampling requirements for a histometric assessment of progression in low grade and high grade prostatic intraepithelial neoplasia (PIN) lesions. STUDY DESIGN: Images of whole glands from normal prostates, low grade PIN lesions and high grade PIN lesions were digitized. The images were processed by a machine vision system and automatically segmented, and a number of histometric characteristics descriptive of the disruption of the basal cell layer were extracted. Next, high-resolution images of secretory cell nuclei still facing or no longer facing intact segments of the basal cell layer were recorded and karyometrically analyzed. RESULTS: For the characterization of an individual lesion a minimum of 20-30 glands should be analyzed to provide an estimate of a progression index. Then, a change in progression, or due to regression, of approximately 16% can be documented. The disruption of the basal cell layer is accompanied by statistically highly significant changes in the chromatin texture and spatial distribution in secretory cell nuclei no longer facing an intact segment of that layer. CONCLUSION: Automated histometry by machine vision can provide valuable quantitative data for diagnostic assessment and for monitoring the efficacy of chemopreventive treatment.

Nuclear chromatin texture in prostatic lesions. I. PIN and adenocarcinoma.

OBJECTIVE: To document changes in the chromatin pattern in secretory cell nuclei from prostates with prostatic intraepithelial neoplasia (PIN) or adenocarcinoma. STUDY DESIGN: High-resolution images of nuclei were recorded, and a set of features descriptive of the chromatin texture and spatial distribution was computed. From this data set, features undergoing a monotonic trend of progression were selected and plotted to reveal trends in lesion progression. RESULTS: The nuclear chromatin in secretory cells in prostates with either PIN or malignant adenocarcinoma undergoes distinct and statistically significant changes in its texture and spatial distribution. Two trends of progressive change were observed. First, the values of a number of features descriptive of the clumpiness of the chromatin increase from values found in normal prostates to those recorded for nuclei from low grade to high grade PIN lesions. The second trend is a decrease in the values of the same features from those found in nuclei from high grade PIN still facing an intact basal cell layer to those no longer facing such a layer. This may be the first detectable step in progression towards development of a malignant lesion. There is a further decrease in nuclei in glands immediately adjacent to adenocarcinoma and in malignant lesions themselves. CONCLUSION: The described changes may lend themselves to the monitoring of lesion progression or of response to treatment or to chemopreventive intervention.

Nuclear chromatin texture in prostatic lesions. II. PIN and malignancy associated changes.

OBJECTIVE: The objective of this study was to identify and document prostatic intraepithelial neoplasia (PIN) and malignancy associated changes in secretory cell nuclei from visually normal appearing tissue regions of prostates harboring PIN or adenocarcinoma. STUDY DESIGN: High-resolution digitized images of nuclei were recorded in histologically normal appearing tissue regions at defined distances from the margin of PIN or malignant lesions. Features descriptive of nuclear chromatin texture were computed and used to derive a discriminant function score for each nucleus. RESULTS: Secretory cell nuclei in prostates harboring either PIN or adenocarcinoma were shown to have statistically significantly different chromatin texture from secretory cell nuclei recorded in prostates free from any such lesion. The expression of PIN or malignancy associated changes was documented for distances up to 10 mm from the margin of a lesion. CONCLUSION: The finding of characteristic changes in nuclear chromatin texture of nuclei from histologically normal appearing tissue in prostates with PIN or adenocarcinoma offers the potential for higher sensitivity of detection of such lesions and for earlier detection of changes potentially preceding the development of clinically significant disease.

Chromatin texture signatures in nuclei from prostate lesions.

OBJECTIVE: To characterize nuclei from prostatic lesions in a highly specific manner by developing a nuclear chromatin texture signature and to characterize lesions by means of their composition of nuclei with diverse degrees of deviation from normal. STUDY DESIGN: High-resolution digitized imagery of nuclei from normal prostates, from prostatic neoplastic lesions of low and high grade and from histologically normal appearing regions of prostates with low and high grade prostatic intraepithelial neoplasia (PIN) lesions were recorded. A set of 65 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus. These features were arranged and processed to form a distinctive signature. A distance metric from "normal" was defined and computed for each nucleus. RESULTS: Profiles of feature values can, after suitable scaling, be presented as distinctive feature value signatures. For many practical applications, profiles based on a standardized distance from normal nuclei may be more useful. Such profiles allow the derivation of a progression curve, showing increasing distances for diagnostic groups with increasing lesion progression up to high grade PIN lesions. Within each diagnostic group different cases show distinctive distributions of nuclei with differing degrees of deviation from normal, allowing the derivation of a lesion signature. CONCLUSION: Nuclear chromatin texture signatures may be of value for the characterization of both nuclei and lesions. They are based on a more comprehensive use of information offered by the nuclear chromatin pattern than that included in classification methods. While these signatures offer a more specific characterization of a clinical sample, they also are subject to more variability within a diagnostic category. This may not be due to randomness but may reflect some actual differences between lesions.

Nuclear morphometry in solar keratosis.

OBJECTIVE: To carry out a feasibility study for the development of procedures for the objective characterization and grading of solar keratotic skin lesions. STUDY DESIGN: Imagery from sections of skin shave biopsies from 12 light-skinned individuals were digitized. A minimum of 25 nuclei from a solar keratotic lesion and 25 nuclei from a location in histologically normal appearing skin adjacent to the lesion were recorded for each case. Values of karyometric features were computed, and a discriminant function distinguishing normal nuclei from nuclei exhibiting solar irradiation damage was derived. RESULTS: Approximately 50% of nuclei in solar keratotic lesions were markedly affected by solar irradiation, but even in biopsies from histologically normal appearing skin, 3-30% of nuclei showed signs of such damage. Nuclei from solar keratotic lesions exhibiting such damage had numerous morphometric and karyometric features commonly found in malignant cells. The state of progression of a solar keratotic lesion can be graded by a plot of proportion of nuclei exhibiting solar damage versus the average discriminant function score of the most affected nuclei. This plot provides a monotonically rising progression curve and a numeric grading score. CONCLUSION: Karyometry of nuclei from skin biopsies allows objective assessment of the progression of solar keratotic lesions. Similarity of feature values in nuclei from solar keratotic lesions to those in malignant lesions was noted. The progression curve derived in this study could serve to measure the efficacy of chemopreventive or therapeutic intervention.

Effect of a patient's sex on the timing of thrombolytic therapy.

STUDY OBJECTIVE: We sought to determine whether a patient's sex independently influences the interval from emergency department arrival to the initiation of thrombolytic therapy in acute myocardial infarction (AMI). METHODS: We conducted a retrospective cohort study in two suburban EDs, one at a 929-bed tertiary care teaching hospital and the other at a 189-bed community hospital. Only patients found to be having an ST-segment-elevated AMI on their first ECG who were treated with a thrombolytic agent in the ED were eligible. We excluded patients who arrived at the ED after cardiac arrest or with a known AMI. We used as the main outcome measure the interval from ED arrival to initiation of thrombolytic therapy. Secondary outcome variables included time elapsed before ECG, interval between ECG and treatment, and 1-year mortality. RESULTS: Entry criteria were satisfied by 328 patients. The 88 women experienced a mean 23-minute delay to treatment initiation compared with men (P < .01). This observation is not accounted for by age, race, time of day, medical history, sex of the physician, type of thrombolytic agent, hospital, or triage category. The longest delays were found in women treated by female physicians, although female physicians also waited longer than male physicians to administer thrombolytic therapy to men. The mean time elapsed before the first ECG was also 6 minutes longer for women (P < .01) Women had an increased 1-year mortality rate that was fully explained by their advanced age at the time of AMI. CONCLUSION: We infer that a patient's sex may play a significant role in the observed delay in treatment for women. Our data, coupled with previously published work, strongly suggest a systematic negative effect for women in their interaction with the health care system during AMI. We suggest that variables other than systems issues affect the time elapsed before thrombolytic therapy.

A new method for identifying the depth of insertion of tracheal tubes.

When a patient's lungs require mechanical ventilation, a plastic breathing tube (tracheal tube, TT) must be inserted through the vocal cords and into the trachea. Although insertion of the TT is a routine procedure, determining the correct depth of insertion is difficult clinically, and may require a chest radiograph. We investigated the accuracy of a simple clinical method for inserting a TT to the correct depth. Typically, an inflatable cuff surrounds the distal circumference of the TT to occlude the gap between TT and tracheal wall. Our technique involves pressing gently with one finger on the front of the lower part of the neck to locate the center of the cuff. We hypothesized that a) a palpating finger can identify the cuff through the tracheal wall, and b) if placed using this technique, the TT will be correctly positioned in the trachea. We studied 79 patients in whom TTs were inserted for general anesthesia. TTs were inserted to a depth determined by the palpation technique. We developed a stylet incorporating a magnetic reed switch which could be inserted through the TT. A magnet with specific field characteristics was passed along the front of the neck to locate the reed switch and confirm the location of the cuff. The TT position in the trachea was then examined with a fiberoptic scope. The palpation technique resulted in optimal positioning of the TT in all subjects and could save approximately $14,268/year in chest radiograph costs in our institution.

High fecundity rates in donor oocyte recipients and in-vitro fertilization surrogates using parenteral oestradiol valerate.

Ovum donation and in-vitro fertilization (IVF) surrogacy can help couples with difficult infertility problems achieve pregnancy. Most centres using oral oestrogens and oestradiol patches report pregnancy rates in the range of 30% per cycle. Parenteral oestradiol valerate has pharmacological properties that make it an attractive option for preparing the endometrium in the recipients undergoing these procedures. When the egg providers were under age 35 years, and using oestradiol valerate in the recipients, we achieved a 61% clinical pregnancy rate in 62 cycles. These improved results suggest that parenteral oestradiol valerate should be used to prepare the endometrium in recipients, and that the hormonal milieu of the endometrium plays an important role in the higher implantation rates obtainable in ovum donor and IVF surrogate cycles.

Discrimination between human T and B lymphocytes by computer analysis of digitized data from scanning microphotometry. II. Discrimination and automated classification.

Human B and T lymphocytes were purified and stained according to the Feulgen procedure. Stained preparations were scanned on a microphotometer and the digitized images were processed by analytical programs on a computer. Features of the cells relating to the chromatin distribution were extracted. Computer algorithms automatically derive classification rules and a machine recognition of B cells and T cells results in better than 80% correct assignments. The image data reveal a rich feature structure within both the purified B and T cell populations. Each population appears to contain several subpopulations of cells with distinctive and different chromatin texture.

Discrimination between human T and B lymphocytes and monocytes by computer analysis of digitized data from scanning microphotometry. I. Chromatin distribution patterns.

Digitized images of Feulgen-stained normal human B and T lymphocytes and monocytes were analyzed by computer and microphotometry. The algorithms assessed the chromatin distribution patterns. A substantial number of parameters descriptive of the chromatin distributions were found to show statistically highly significant differences between B and T cells and monocytes. Although the effects of a number of biologic variables, such as cell cycle phase and immune stimulation, need to be carefully evaluated, the preliminary results indicate potential for automatic classification and subclassification of human B and T lymphocytes in normal and disease states.

Effect of summer heat stress on serum luteinizing hormone and progresterone values in Holstein-Friesian cows in Arizona.

Serum-luteinizing hormone and progesterone values were measured in lactating and nonlactating Holstein-Friesian cows to evaluate their relationship with reduced fertility observed during hot summer months in Arizona. The stress of hot weather had no effect on frequency of preovulatory increase of luteinizing hormone nor on the interval between the preovulatory increase and ovulation in either lactating or nonlactating cows. Progesterone values were significantly (P less than 0.05) increased in lactating cows which became hyperthermic during hot weather, yet progesterone values did not change in nonlactating cows which had remained homeothermic. A similar relationship was observed between fertility and serum progesterone values, and between fertility and degree of thermal stress caused by hot weather. Decreased fertility and increased serum progesterone values were associated with increased environmental temperature and hyperthermia.