A new immunomodulatory therapy for severe sepsis: Ulinastatin Plus Thymosin {alpha} 1.

OBJECTIVES: To study the effect of immunomodulatory therapy with ulinastatin plus thymosin alpha( 1) on septic patients. METHOD: A total of 56 sepsis patients were randomized into a treatment group, receiving immunomodulatory therapy, and a placebo group, a placebo. Acute Physiology and Chronic Health Evaluation II scores, clinical data, lymphocyte subsets, immunological indexes, and coagulation parameters were determined before admission and on the 3rd, 8th, and 28th day after admission to the Intensive Care Unit. RESULTS: The treatment group experienced a 78% cumulative survival, the placebo group experienced a 60% cumulative survival; the survival difference was mirrored by Acute Physiology and Chronic Health Evaluation II scores and more quickly improved leukocyte counts, lymphocyte counts, coagulation parameters, and cytokine levels in the treatment. CONCLUSIONS: Combined immunomodulatory therapy with ulinastatin plus thymosin alpha(1) appears to yield improved survival for patients with sepsis; this finding should be verified in larger clinical trials.

Survivin expression in ovarian cancer.

AIM: To examine the expression of survivin in benign ovarian tumors, ovarian carcinomas of different stages. METHODS: We screened the expression of survivin mRNA by reverse transcription polymerase chain reaction in 114 ovarian tissue samples. Quantitative real-time PCR was used to estimate survivin mRNA levels in the samples with positive survivin expression. RESULTS: No survivin mRNA was expressed in all normal ovarian specimens, while it appeared in 73% of ovarian carcinomas, 47% of borderline ovarian carcinomas and 19% of benign ovarian tumors. The survivin mRNA expression rate was positively associated with clinical stage (P = 0.026) and differentiation grade (P = 0.049). There was notably statistically significant difference in the survivin mRNA expression rate dependent on different histological types (serous, mucinous, endometrioid, P = 0.008), but not - dependent on lymph node metastasis (P = 0.921) and ascites (P = 0.87). In tissues with positive expression of survivin, we also found that mean survivin mRNA expression levels were higher in ovarian carcinomas than that in benign ovarian tumors and borderline ovarian carcinoma tissues (P < 0.001). Among ovarian carcinomas, the high survivin mRNA expression levels correlated with the clinical stages, differentiation grade, lymph node metastasis, but not - with ascites and histological type. CONCLUSION: Our study suggest that survivin is associated with progression of ovarian carcinoma.

Laparoscopic re-exploration in mechanical bowel obstruction after laparoscopic gastric bypass for morbid obesità.

AIM: This study reports a series of 7 patients who experienced small-bowel obstruction (SBO) after laparoscopic gastric bypass (LGBP). METHODS: Between July 2001 and June 2004, 211 patients underwent surgery for morbid obesity in 2 different institutions and 7 of them required reoperative laparoscopic surgery or laparotomy for mechanical SBO. RESULTS: Seven patients in the series (3%) developed a postoperative bowel obstruction requiring operative management. Their mean body mass index was 49 (range: 38-65) and the average age was 48 years (range 29-60). Six (86%) had undergone an initial LGBP. One (14%) had been converted to open surgery because of the presence of thick adhesions. One percent of the patients (14%) had undergone abdominal surgery prior to gastric bypass. The most common cause of SBO was internal hernia through a mesenteric defect (57%), followed by adhesions (14%), obstruction at the entero-enterostomy (14%) and Petersen hernia (14%). The obstruction was managed laparoscopically. Small-bowel resection was required in 14% with no death encountered after the second revision of the entero-enterostomy. Recovery time was less than 72 h after laparoscopic approach and more than 92 h following the open procedure. CONCLUSIONS: Laparoscopic surgical correction of SBO following LGBP in morbidly obese patients is feasible. Reoperation of morbidly obese patients after LGBP can be achieved successfully through laparoscopic techniques.

A single proposed algorithm for the surgical treatment of hepatic hemorrhage.

Angiographic embolization safely and effectively controls hemorrhage from the liver. Contrasting algorithms and protocols have, however, created confusion as to how and when to use this procedure. After performing a Medline search, a proposed protocol for the use of angiographic embolization was created. This algorithm, which focuses on general hepatic response to injury, not to any particular disease, is best applied in busy tertiary hospitals. The generalized applicability of the proposed protocol may allow for a more uniform, easily remembered, and effective treatment of liver hemorrhage.

Influence of obesity on the risk of developing colon cancer.

Obesity is a risk factor for many diseases. Thirty per cent of Americans are viewed as super obese; therefore, we need to find a solution. We already know about the diseases associated with obesity such as high blood pressure, diabetes, sleep apnoea, etc. Lately, there has been an increased interest in understanding if cancer is related to obesity. In this paper, we review the incidence of colon cancer and obesity. Insulin is the best established biochemical mediator between obesity and colon cancer. Hyperinsulinaemia, such as occurs in type II diabetes, is important in the pathogenesis of colon cancer. All adipose tissue is not equal. Visceral abdominal fat has been identified as the essential fat depot for pathogenetic theories that relate obesity and colon cancer. The genders differ as regards to how the relationship between obesity and colon cancer has been evaluated. Obesity imposes a greater risk of colon cancer for men of all ages and for premenopausal women than it does for postmenopausal women. Regular exercise reduces the risk of developing colon cancer and the risk of death from colon cancer should it develop. We believe that a combination of waist circumference (WC) and body mass index (BMI) measurements is recommended to assess the obesity related risk of developing colon cancer. Radiographic assessments of visceral abdominal fat may eventually prove to be the best means of assessing a patient's obesity related risk of developing colon cancer. Although WC is better established as a measure of obesity than BMI, the evidence for colon cancer risk is not secure on this point; combining BMI and WC measurements would appear, at present, to be the wisest approach for colon cancer risk assessment. Doctors who wish to decrease their patients' risk of dying of colon cancer should advise weight loss and exercise. Conversely, physicians and public health authorities should consider both exercise and obesity when designing colon cancer screening protocols. Morphometric cut offs should be adjusted, if possible, for age, sex, ethnicity, and height.

The ASCUS : SIL ratio and the reference laboratory pathologist.

The atypical squamous cells of undetermined significance (ASCUS) : squamous intraepithelial lesion (SIL) ratio was proposed to monitor laboratory use of the ASCUS diagnosis. This study addresses problems associated with comparing pathologists by this means. An intuitive example showed the ASCUS : SIL ratio depends on the prevalence of smears from patients who actually have SIL. In this study of 2000 cervical smears, each of five pathologists made 400 diagnoses. Differences among proportions of SIL diagnoses were statistically significant; differences among proportions of ASCUS diagnoses were not. Had an ASCUS : SIL ratio upper limit of 3.0 been used, two pathologists would have been misidentified as having high ASCUS diagnosis rates. Unlike the situation for laboratories, potential variability in SIL prevalence requires caution in the use of this ratio in assessing pathologists. An alternative measure that is independent of prevalence, the ASCUS : SIL odds ratio, is posited.

Bladder washing cytology. Comparison of two analytic methods and two proposed quantitative criteria for carcinoma in situ.

OBJECTIVE: To compare bladder washing cytology preparations created by the Nucleopore filter and slide centrifuge techniques and to evaluate a marker for carcinoma in situ (CIS). STUDY DESIGN: Nucleopore filter and slide centrifuge preparations from 27 patients with urothelial carcinoma were compared and used to create two criteria for CIS. To study reproducibility, three observers evaluated 25 filter preparations for these CIS criteria. RESULTS: The filter technique displayed more better-preserved single cancer cells (P = .02) and a higher percent group count (the number of cancer cell groups divided by the sum of the number of single cancer cells plus the number of cancer cell groups) (P = .005) than did the cytocentrifuge technique. The initial study showed that patients with many single tumor cells and lower percent group counts were more likely to have CIS than patients without this combined condition (P = .001). This CIS marker had moderate reproducibility (kappa = 0.47 +/- 0.12). CONCLUSION: The filter technique had better cellular recovery and preservation of tumor cells than did the centrifuge technique. Quantitative cytologic criteria proposed in this study may be an indication that CIS may be present; improved sensitivity and specificity may be obtained if they are combined with other criteria.

Tissue calcification after orthotopic liver transplantation. An autopsy study.

A retrospective review of 25 patients who underwent orthotopic liver transplantation was performed to relate the prevalence and preferred sites of microscopic calcium deposition seen at autopsy to clinical parameters, namely, hypercalcemia, hypercalcemia, hyperphosphatemia, and renal failure. Microscopic foci of calcification were noted in 84% of patients, and hypercalcemia was noted in 68%. Multiple regression analysis demonstrated that the number of microscopically calcified organs depended in part on the peak total serum calcium level and the duration of hypercalcemia and that the peak total serum calcium level depended in part on the peak phosphorus level and the quantity of calcium administered intraoperatively. Univariate analysis showed that peak phosphorus level was partially dependent on the peak creatinine level. The data suggest that hypercalcemia and postoperative ectopic calcification are common and related occurrences following hepatic transplantation and that intraoperative manipulations of serum calcium levels and renal failure partially, but not entirely, account for this phenomenon.

Immunoperoxidase staining of cervicovaginal smears after radiotherapy.

Cervicovaginal smears from 2 women with postirradiation dysplasia, 4 women with postirradiation squamous cell carcinoma of the cervix, 30 women with irradiation atypia and 5 healthy, nonirradiated women were stained immunohistochemically with six keratin antibodies. For four of the antibodies--CK19 (BA17), EMA, PKK-1 and CAM 5.2--squamous cells showing irradiation atypia, postirradiation dysplasia or postirradiation squamous cell carcinoma were more likely to stain positively than were nonirradiated squamous cells. For three of the antibodies in which multiple squamous cells stained positively, the proportion of squamous cells showing postirradiation dysplasia or postirradiation squamous cell carcinoma staining strongly was equal to or greater than the corresponding overall proportion for squamous cells showing irradiation atypia. This was statistically significant with only one antibody, PKK-1. No statistically significant differences were seen in staining of irradiated and nonirradiated squamous cells by MAK-6 and AE1:AE3. The data show that some keratin antigens are more often expressed in the irradiated groups and that there may be differences in the degree of antigen expression between squamous cells showing postirradiation dysplasia or postirradiation squamous cell carcinoma and squamous cells showing irradiation atypia.

Clonal cytogenetic abnormalities in Hodgkin's disease.

Cytogenetic studies of Hodgkin's disease (HD), in contrast to those of non-Hodgkin's lymphoma (NHL), have been limited to small numbers of cases with infrequently recurring aberrations, underscoring the need for additional studies in establishing a coherent cytogenetic picture of HD. Over a 6 1/2-year period, we received 95 specimens of HD for cytogenetic analysis. Analyzable chromosome preparations were obtained in 70 cases, of which 57 (81%) showed only normal metaphases. In the remaining 13 cases (19%), karyotypic abnormalities were observed that were nonclonal in 3 and clonal in 10. The latter 10 cases included 6 of the nodular sclerosis subtype, 3 mixed cellularity, and 1 lymphocyte-depleted; 8 of the specimens were obtained pretreatment and 2 posttreatment. Two of the cases had a clonal numerical aberration, monosomy 17 in one and trisomy 13 in the other, as their sole abnormality. The remaining 8 cases showed complex karyotypes with multiple structural rearrangements; in 3 of these, the abnormal clone was near-tetraploid. Bands involved more than once included 1p36, 1q21, and 4q35, each in 2 cases. Arms involved more than once included 6q (6q13,6q23), 9p (9p13,9p21), and 5q (5q15,5q35). Three patients had loss of part or all of 6q (del(6)(q13),del(6)(q23),i(6p). Bands 14q32 and 18q21 were not involved in any case, contrary to some previous reports. Our results confirm the frequent occurrence of 1p, 1q, and 6q abnormalities in HD. In addition, we have identified a 5q35 breakpoint, which has recently been shown to be highly specific for Ki-1-positive NHL in a case of typical nodular sclerosis HD. Its presence in HD may represent a cytogenetic link between the two entities, which are immunophenotypically related but clinically and histologically distinct.

Automated analysis of rat breast tumors. Comparison of four methods.

Chemically-induced malignant rat breast tumors pose diagnostic dilemmas since the majority are well-differentiated, noninvasive papillary lesions that are barely distinguishable from benign papillary lesions. This study compared several automated modalities to see which best separated benign from malignant breast tumors. Thirty-three carcinogen-induced rat breast tumors (13 adenomas, 10 papillary carcinomas and 10 invasive carcinomas) were evaluated by static (image) cytometry (ICM) of integrated optical density, by flow cytometry (FCM) and by two automated morphometric protocols, contextual analysis and single-gland analysis. DNA ploidy analysis, by either ICM or FCM, did not discriminate between the benign and malignant tumors. Contextual analysis correctly identified 11 of 13 benign and 17 of 20 malignant lesions (P less than .01). Single-gland analysis correctly identified all 13 benign and 17 of 20 malignant lesions (P less than .01). No method distinguished invasive from noninvasive carcinomas. The data suggest that architectural features are more important than nuclear features in differentiating benign from malignant rat breast tumors.

How many patients are necessary to assess test performance?

Test performance characteristics are important in assessing the clinical usefulness of laboratory tests and serve as a basis for comparing one test to another. Statistical comparisons of performance characteristics are meaningful only when they can detect medically important differences; that is, when they provide adequate statistical power. This requires choosing the appropriate sample size in determining the performance characteristics of interest. Using standard formulas, we designed tables that provide such sample size requirements. Example problems of sample size determination in laboratory test comparisons are given. Used appropriately, this approach should result in better studies of laboratory tests and fewer meaningless negative studies.

Simultaneous determination of local cerebral glucose utilization and blood flow by carbon-14 double-label autoradiography: method of procedure and validation studies in the rat.

Validation studies were undertaken to establish a computer-assisted double-label autoradiographic strategy employing [14C]2-deoxyglucose ([14C]2DG) and [14C]iodoantipyrine ([14C]IAP) to measure local CMRglu (LCMRglu) and CBF (LCBF). An organic solvent was used to extract the majority of IAP between first and second film exposures. In contrast to previously published data, all solvents tested produced partial losses of 2DG from tissue, and all allowed 2-6% of IAP to persist even after 5-day washes. Technical-grade chloroform permitted equal retention of unmetabolized and metabolized 2DG. A linear model was established, which was insensitive to the changes in tissue self-absorption that were shown to occur with chloroform extraction. Propagated error in computing tissue [14C]2DG and [14C]IAP was reduced by maximizing IAP extraction (by longer solvent wash times) and by administering 2.5 times as much IAP as 2DG. Fractional 2DG retention was measured in single-label 2DG sections placed on the films, and fractional IAP retention was evaluated by an optimization procedure. With this strategy, double-label values for LCMRglu and LCBF in anesthetized rats agreed with values obtained in matched single-label series to within 5%. The coefficients of variation for the double- and single-label LCMRglu data were virtually identical, whereas the coefficient of variation for double-label LCBF was 1.8 times that of single-label LCBF. The double-label strategy permitted pixel-by-pixel measurement and video display of the LCMRglu/LCBF ratio; the mean value among structures was 0.472 mumol/ml. With proper attention to methodological detail, this double-label strategy shows great promise for routine laboratory application.

Induction of reproducible brain infarction by photochemically initiated thrombosis.

We have used a photochemical reaction in vivo to induce reproducible thrombosis leading to cerebral infarction in rats. After the intravenous injection of rose bengal, a potent photosensitizing dye, an ischemic lesion was formed by irradiating the left parietal convexity of the exposed skull for 20 minutes with green light (560 nm) from a filtered xenon arc lamp. Animals were allowed to survive from 30 minutes to 15 days after irradiation. Early microscopic alterations within the irradiated zone included the formation of thrombotic plugs and adjacent red blood cell stasis within pial and parenchymal vessels. Scanning electron microscopy revealed frequent platelet aggregates adhering to the vascular endothelium, often resulting in vascular occlusion. Carbon-black brain perfusion demonstrated that occlusion of vascular channels progressed after irradiation and was complete within 4 hours. Histopathological examination at 1, 5, and 15 days revealed that the associated infarct evolved reproducibly through several characteristic stages, including a phase of massive macrophage infiltration. Although cerebral infarction in this model is initiated by thrombosis of small blood vessels, the fact that the main pathological features of stroke are consistently reproduced should permit its use in assessing treatment regimens. Further, the capability of producing infarction in preselected cortical regions may facilitate the study of behavioral, functional, and structural consequences of acute and chronic stroke.