Identifying Factors Predicting Response to Endoscopic Management of Chronic Pancreatitis Secondary to Pancreas Divisum.

INTRODUCTION: Appropriately selecting patients with chronic pancreatitis associated with pancreas divisum (PD) for endoscopic retrograde cholangiopancreatography (ERCP)-based therapy versus surgery remains difficult. The objective of this study was to identify factors that predict success or failure of ERCP for treatment of chronic pancreatitis in PD. METHODS: Patients undergoing ERCP for a diagnosis of PD and pancreatitis between 2008 and 2016 were identified and grouped according to whether they required one or two ERCPs or three or more ERCPs. Groups were compared along demographic, diagnostic, laboratory, ERCP-related, and outcome variables. RESULTS: Patients requiring 1-2 ERCPs were less likely to have back pain on initial presentation (4 vs. 24%, p = 0.02) and less likely to have a dilated bile duct on imaging prior to their first ERCP (8 vs. 30%, p = 0.04) than those requiring 3+ ERCPs. Patients requiring 1-2 ERCPs were also less likely to eventually require operative intervention for treatment of their chronic pancreatitis than those requiring 3+ ERCPs (24 vs. 44%, p = 0.047). On multivariable analysis, a dilated bile duct (odds ratio (OR) = 6.0, 95% confidence interval (CI) = 1.01-36.0, p = 0.048) was independently associated with requiring 3+ ERCPs. Back pain (OR = 6.3, 95% CI = 0.73-54.2, p = 0.09) trended toward but did not reach statistical significance for being independently associated with requiring 3+ ERCPs. CONCLUSIONS: The success of endoscopic treatment of chronic pancreatitis in patients with PD is dependent on proper patient selection. Patients with a dilated bile duct and back pain upon presentation may not respond well to endoscopic treatment alone and are more likely to eventually require operative intervention. Consideration should be given to early operative intervention in these patients.

Comparing the efficacy of initial percutaneous transhepatic biliary drainage and endoscopic retrograde cholangiopancreatography with stenting for relief of biliary obstruction in unresectable cholangiocarcinoma.

BACKGROUND: In patients with cholangiocarcinoma (CC), management of biliary obstruction commonly involves either up-front percutaneous transhepatic biliary drainage (PTBD) or initial endoscopic retrograde cholangiopancreatography (ERCP) with stent placement. The objective of the study was to compare the efficacy and of initial ERCP with stent placement with efficacy of initial PTBD in management of biliary obstruction in CC. METHODS: A single-center database of patients with unresectable CC treated between 2006 and 2017 was queried for patients with biliary obstruction who underwent either PTBD or ERCP. Groups were compared with respect to patient, tumor, procedure, and outcome variables. RESULTS: Of 87 patients with unresectable CC and biliary obstruction, 69 (79%) underwent initial ERCP while 18 (21%) underwent initial PTBD. Groups did not differ significantly with respect to age, gender, or tumor location. Initial procedure success did not differ between the groups (94% ERCP vs 89% PTBD, p = 0.339). Total number of procedures did not differ significantly between the two groups (ERCP median = 2 vs. PTC median = 2.5, p = 0.83). 21% of patients required ERCP after PTBD compared to 25% of patients requiring PTBD after ERCP (p = 1.00). Procedure success rate (97% ERCP vs. 93% PTBD, p = 0.27) and rates of cholangitis (22% ERCP vs. 17% PTBD, p = 0.58) were similar between the groups. Number of hospitalizations since initial intervention did not differ significantly between the two groups (ERCP median = 1 vs. PTC median = 3.5, p = 0.052). CONCLUSIONS: In patients with CC and biliary obstruction, initial ERCP with stent placement and initial PTBD both represent safe and effective methods of biliary decompression. Initial ERCP and stenting should be considered for relief of biliary obstruction in such patients in centers with advanced endoscopic capabilities.

Nutritional composition and in vitro digestibility of grass and legume winter (cover) crops.

In dairy farming systems, growing winter crops for forage is frequently limited to annual grasses grown in monoculture. The objectives of this study were to determine how cropping grasses alone or in mixtures with legumes affects the yield, nutritional composition, and in vitro digestibility of fresh and ensiled winter crops and the yield, nutritional composition, and in vitro digestibility of the subsequent summer crops. Experimental plots were planted with 15 different winter crops at 3 locations in Virginia. At each site, 4 plots of each treatment were planted in a randomized complete block design. The 15 treatments included 5 winter annual grasses [barley (BA), ryegrass (RG), rye (RY), triticale (TR), and wheat (WT)] in monoculture [i.e., no legumes (NO)] or with 1 of 2 winter annual legumes [crimson clover (CC) and hairy vetch (HV)]. After harvesting the winter crops, corn and forage sorghum were planted within the same plots perpendicular to the winter crop plantings. The nutritional composition and the in vitro digestibility of winter and summer crops were determined for fresh and ensiled samples. Growing grasses in mixtures with CC increased forage dry matter (DM) yield (2.84 Mg/ha), but the yield of mixtures with HV (2.47 Mg/ha) was similar to that of grasses grown in monoculture (2.40 Mg/ha). Growing grasses in mixtures with legumes increased the crude protein concentration of the fresh forage from 13.0% to 15.5% for CC and to 17.3% for HV. For neutral detergent fiber (NDF) concentrations, the interaction between grasses and legumes was significant for both fresh and ensiled forages. Growing BA, RY, and TR in mixtures with legumes decreased NDF concentrations, whereas growing RG and WT with legumes did not affect the NDF concentrations of either the fresh or the ensiled forages. Growing grasses in mixtures with legumes decreased the concentration of sugars of fresh forages relative to grasses grown in monoculture. Primarily, this decrease can be attributed to low concentrations of sugars of mixtures with HV (10.5%). Growing grasses in mixtures with legumes reduced the fiber digestibility of both winter crops (75.7% to 72.8% NDF). Growing grasses in mixtures with legumes did not affect estimated DM yield, nutritional composition, or digestibility of the succeeding summer crops. In conclusion, growing grasses in mixtures with legumes as winter forage crops can increase forage estimated DM yields and its nutritional quality in dairy farming sytems.

Mantle cell lymphoma: primary oral presentation.

Mantle-cell lymphoma is an uncommon lymphoid malignancy of B-cells. It is often aggressive and prognosis is poor. A 69-year-old gentleman with a history of ischaemic heart disease was referred from primary care with a painless right floor of mouth swelling that had been present for 1 month. He otherwise completely asymptomatic. Incisional biopsy of the lesion was undertaken and marker studies demonstrated mantle cell lymphoma. Positron emission tomography-computed tomography and bone marrow biopsy showed widespread but low volume involvement. The patient was referred to the haematology multidisciplinary team for further assessment and treatment.

Scleroderma renal crisis sine scleroderma in pregnancy: a case report.

Scleroderma renal crisis has been documented as the presenting manifestation of systemic sclerosis sine scleroderma in pregnancy only once in the literature. Unfortunately, since scleroderma renal crisis in sine scleroderma pregnant patients is so rare, that patient expired. We present a case of a sine scleroderma pregnant patient with an initial manifestation of scleroderma renal crisis surviving due to successful diagnosis and treatment.

Scleroderma renal crisis in pregnancy associated with massive proteinuria.

Scleroderma renal crisis is a well-recognized complication of systemic sclerosis (SSc) usually occurring early in the course of the disease in patients with diffuse skin involvement. We report the diagnostic challenge of a case of scleroderma renal crisis associated with massive proteinuria at approximately 20 weeks gestation in a pregnant patient with diffuse cutaneous systemic sclerosis.

Changes in vascular responsiveness to a thromboxane mimetic in endotoxin tolerance.

Our previous studies have demonstrated that peritoneal macrophages obtained from endotoxin-tolerant rats exhibit altered cellular activation by endotoxin, possibly involving changes in guanine nucleotide regulatory (G) protein-coupled signal transduction pathways. Endotoxin-tolerant rats also exhibit cross tolerance and altered hemodynamic responses to thromboxane (Tx)A2 mimetics, suggesting potential changes in vascular responsiveness. We tested the hypothesis that endotoxin tolerance results in vascular hyporesponsiveness to a TxA2 mimetic via alterations in the TxA2 receptor, G protein function, and/or second messenger production. Rats were rendered endotoxin tolerant by increasing sublethal consecutive doses of Salmonella enteritidis endotoxin (100 to 5000 micrograms/kg, i.p.) for 4 days. The animals were sacrificed 2 days after the final dose of endotoxin for removal of aortas. Contractile responses of aortic rings to U46619, a TxA2 agonist, were assessed in control and tolerant rats. The EC50 values for U46619 were 14.8 +/- 6.6 nM and 32.3 +/- 3.1 nM (n = 5-7), (P < 0.05) for control and tolerant rats, respectively. Crude membranes were prepared from aortas of control and tolerant rats, and binding of I-BOP TxA2/PGH2 receptor agonist, [1S-(1 alpha, 2 beta (5Z), 3 alpha (1E, 3S*), 4 alpha)]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7- oxabicyclo-[2.2.1]heptan-2-yl]-5-heptenoic acid (I-BOP), a TxA2 agonist, was assessed by Scatchard analysis. I-BOP binding to the TxA2 receptor was saturable and revealed a single class of TxA2 receptors for both groups. There was no significant difference in control (n = 7) compared with tolerant (n = 5) Kd values (2.1 +/- 0.2 vs. 2.4 +/- 0.9 nM, respectively), or Bmax (31 +/- 6 vs. 28 +/- 12 fmol/mg protein, respectively). To assess potential changes in G protein function, aortic membrane GTpase activity was determined. GTPase activity in tolerant membranes was significantly reduced (P < 0.05) compared with control membranes (309 +/- 23 (n = 5) vs. 440 +/- 32 (n = 7) pmol/mg/protein/min, respectively). However, U46619-stimulated phosphoinositide production was similar in vascular tissue from control and tolerant rats. These observations suggest that the decreased contractile response to TxA2 mimetics in endotoxin tolerance does not result from a change in receptor number, affinity of TxA2 receptors, or changes in phosphatidylinositol metabolism but is associated with decreased vascular G protein function.

Utilization of intravenous tissue-type plasminogen activator for ischemic stroke at academic medical centers: the influence of ethnicity.

BACKGROUND AND PURPOSE: We sought to measure the overall rate of usage of tissue-type plasminogen activator (tPA) for ischemic stroke at academic medical centers, and to determine whether ethnicity was associated with usage. METHODS: Between June and December 1999, 42 academic medical centers in the United States each identified 30 consecutive ischemic stroke cases. Medical records were reviewed and information on demographics, medical history, and treatment were abstracted. Rates of tPA use were compared for African Americans and whites in univariate analysis and after adjustment for age, gender, stroke severity, and type of medical insurance with multivariable logistic regression. RESULTS: Complete information was available for 1195 ischemic stroke patients; 788 were whites and 285 were African Americans: Overall, 49 patients (4.1%) received tPA. In the subgroup of 189 patients without a documented contraindication to therapy, 39 (20.6%) received tPA. Ten (20%) of those receiving tPA had documented contraindication. African Americans were one fifth as likely to receive tPA as whites (1.1% African Americans versus 5.3%; P=0.001), and the difference persisted after adjustment (OR 0.21, 95% CI 0.06 to 0.68; P=0.01). When comparison was restricted to those without a documented contraindication to tPA, the difference remained significant (OR 0.24, 95% CI 0.06 to 0.93; P=0.04). Medical insurance type was independently associated with tPA treatment. After adjustment for ethnicity and other demographic characteristics, those with Medicaid or no insurance were one ninth as likely to receive tPA as those with private medical insurance (OR 0.11, 95% CI 0.02 to 0.17; P=0.003). CONCLUSIONS: tPA is used infrequently for ischemic stroke at US academic medical centers, even among qualifying candidates. African Americans are significantly less likely to receive tPA for ischemic stroke. Contraindications to treatment do not appear to account for the difference.

Combining chondrocytes and smooth muscle cells to engineer hybrid soft tissue constructs.

Engineering new tissues using cell transplantation may provide a valuable tool for reconstructive surgery applications. Chondrocyte transplantation in particular has been successfully used to engineer new tissue masses due to the low metabolic requirements of these cells. However, the engineered cartilaginous tissue is too rigid for many soft tissue applications. We propose that hybrid tissue engineered from chondrocytes and smooth muscle cells could reflect mechanical properties intermediate between these two cell types. In this study, rat aortic smooth muscle cells and pig auricular chondrocytes were co-cultured on polyglycolic acid fiber-based matrices to address this hypothesis. Mixed cell suspensions were seeded by agitating the polymer matrices and a cell suspension with an orbital shaker. After seeding, cell-polymer constructs were cultured in stirred bioreactors for 8 weeks. The cell density and extracellular matrix (collagen, elastin, and glycosaminoglycan) content of the engineered tissues were determined biochemically. After 8 weeks in culture, the hybrid tissue had a high cell density (5.8 x 108 cells/cm(3)), and elastin (519 microg/g wet tissue sample), collagen (272 microg/g wet tissue sample), and glycosaminoglycan (GAG; 10 microg/g wet tissue sample) content. Mechanical testing indicated the compressive modulus of the hybrid tissues after 8 weeks to be 40.8 +/- 4.1 kPa and the equilibrium compressive modulus to be 8.4 +/- 0.8 kPa. Thus, these hybrid tissues exhibited intermediate stiffness; they were less stiff than native cartilage but stiffer than native smooth muscle tissue. This tissue engineering approach may be useful to engineer tissues for a variety of reconstructive surgery applications.

Use of commercial record linkage software and vital statistics to identify patient deaths.

We evaluate the ability of a microcomputer program (Automatch) to link patient records in our hospital's database (N = 253,836) with mortality files from California (N = 1,312,779) and the U.S. Social Security Administration (N = 13,341,581). We linked 96.5% of 3,448 in-hospital deaths, 99.3% for patients with social security numbers. None of 14,073 patients known to be alive (because they were subsequently admitted) was linked with California deaths, and only 6 (0.1%) of 6,444 were falsely identified as dead in the United States file. For patients with unknown vital status but items in the database likely to be associated with high 3-year mortality rates, we identified death records of 88% of 494 patients with cancer metastatic to the liver, 84% of 164 patients with pancreatic cancer, and 91% of 126 patients with CD4 counts of less than 50. Hospital data can be accurately linked with state and national vital statistics using commercial record linkage software.

Sensitive thyrotropin and free thyroxine testing in outpatients. Are both necessary?

BACKGROUND: The appropriate use of specific thyroid function tests to detect thyroid dysfunction remains controversial; some experts recommend both a sensitive thyrotropin (sTSH) test and a free thyroxine (FT4) test, while others recommend an sTSH test alone. OBJECTIVE: To determine how often sTSH and FT4 tests are ordered simultaneously, how often the results are discordant, and under what circumstances a single test of thyroid function may be sufficient to rule out thyroid dysfunction. METHODS: Retrospective descriptive study of all sTSH and FT4 tests performed on adult outpatients during a 6-month period. If both sTSH and FT4 tests were performed on a single serum specimen, the results were classified as concordant (both tests indicating hypothyroidism, hyperthyroidism, or euthyroidism) or discordant. Chart review was performed on patients with normal sTSH results and abnormal FT4 results. RESULTS: A total of 6551 sTSH and 3518 FT4 tests were performed during the study period. Both sTSH and FT4 tests were ordered together on 3143 specimens (48% and 89% of the total number of sTSH and FT4 tests ordered, respectively) from 2629 patients. Of the sTSH results, 69.8% were within the normal range, and 92.7% of the FT4 results were normal. The concordance between sTSH and FT4 results was 74.3%. Among the 1835 specimens with normal sTSH results, FT4 level was low in 11 patients (0.6%; 95% confidence interval, 0.3%-0.9%) and high in 24 (1.3%; 95% confidence interval, 0.8%-1.8%). Chart review did not disclose any instances when an abnormal FT4 results contributed to the treatment of an individual with a normal sTSH result. CONCLUSIONS: The sTSH test alone, and not the combination of sTSH and FT4 tests, should be ordered in most outpatients. An FT4 test should not be routinely ordered if the sTSH result is normal; at our institution this approach would obviate the need for at least half of the FT4 tests performed each year.

Case-mix adjustment using objective measures of severity: the case for laboratory data.

OBJECTIVE: We evaluate the use of routinely gathered laboratory data to subclassify surgical and nonsurgical major diagnostic categories into groups homogeneous with respect to length of stay (LOS). DATA SOURCES AND STUDY SETTING: The source of data is the Combined Patient Experience database (COPE), created by merging data from computerized sources at the University of California San Francisco (UCSF) Medical Center and Stanford University Medical Center for a total sample size of 73,117 patient admissions. STUDY DESIGN: The study is cross-sectional and retrospective. All data were extracted from COPE consecutive admissions; the unit of analysis is an admission. The outcome variable LOS proxies hospital resource utilization for an inpatient stay. Nine (candidate) predictor variables were derived from seven lab tests (WBC, Na, K, C02, BUN, ALB, HCT) by recording the whole-stay minimum or maximum test result. DATA COLLECTION/EXTRACTION METHODS: Patient groups were formed by first assigning to major diagnostic categories (MDCs) all 73,117 admissions. Each MDC was then partitioned into medical and surgical subgroups (sub-MDCs). The 13 sub-MDCs selected for study define a study population of 32,599 patients that represents approximately 45 percent of inpatients. Within each of the 13 sub-MDCs, patients were randomly assigned to one of two data sets in a ratio of 2:1. The first set was used to create, the second to validate, three different LOS predictors. Predictive accuracies of individual DRG classes were compared with those of two alternative classification schemes, one formed by recursive partitioning (the sub-MDC) using only lab test results, the other by partitioning with both lab test results and individual DRGs. PRINCIPAL FINDINGS: For the eight largest sub-MDCs (81 percent of study population), individual DRGs explained 23 percent of the within sub-MDC variance in LOS, laboratory data classes explained 31 percent, and classes derived by considering individual DRGs and laboratory data explained 37 percent. (Each result is a weighted average R2. The average number of LOS classes into which the eight largest sub-MDCs were partitioned were 20, 10, and 10, respectively. Within six of the eight, partitioning on the basis of laboratory data alone explained more within sub-MDC variance than did partitioning into individual DRGs. CONCLUSIONS: Routine lab test data improve the accuracy of LOS prediction over that possible using DRG classes. We note that the improvements do not result from overfitting the data, since the numbers of LOS classes we use to predict LOS are considerably fewer than the numbers of individual DRGs.

Temperature differentials between treatment and pretreatment temperatures correlate with local control following radiotherapy and hyperthermia.

PURPOSE: To evaluate the influence of pretreatment tumor temperatures and the temperature differential between treatment and pretreatment temperatures on local tumor control in patients who underwent combined radiation therapy and hyperthermia. METHODS AND MATERIALS: Mapped intratumoral temperatures were measured immediately prior to and during hyperthermia in 138 hyperthermia fields among 59 patients with nodular (60 fields) or diffuse (78 fields) superficially-located tumors. In the nodular subgroup there were 40 fields with adenocarcinomas (31 breast, two prostate, seven other primary sites), six melanomas, nine squamous cell carcinomas, and five other histologies. The fields with diffuse tumor involvement consisted of 77 adenocarcinomas (67 breast, 10 other) and one melanoma. The maximum, minimum, and average temperatures were determined for both the pretreatment (pTmax, pTmin, pTave) and treatment (Tmax, Tmin, Tave) distributions and the differences, Dm = Tmin-pTmax, and Da = Tmin-pTave, computed. These quantities were averaged over treatments to produce the corresponding mean quantities for each hyperthermia field. Univariate and multivariate analyses were performed to determine treatment and pretreatment parameters which best correlated with the duration of local control. RESULTS: Pretreatment tumor temperatures were significantly lower than the oral temperatures with mean pTmax, mean pTmin, and mean pTave of 36.2 degrees C, 34.2 degrees C, and 35.4 degrees C, respectively. For the adenocarcinomas with diffuse involvement within the hyperthermia field, the covariates best correlating with local control duration on univariate analysis were concurrent radiation dose (p = 0.0026), Dm (p = 0.009), pTmax (p = 0.012) and Da (p = 0.036). Lower pTmax and larger Dm and Da were predictive for longer local control. In multivariate analyses, all thermal parameters lost power, however, the best model included Dm which was significant at the p = 0.040 level. For the nodular subgroup, nonthermal parameters and dichotomized thermal parameters were of prognostic significance for local control. CONCLUSION: For fields diffusely involved with adenocarcinoma significant correlations with duration of local control have been demonstrated both for a) low pretreatment temperatures and b) large differentials between treatment and pretreatment intratumoral temperatures. These correlations were also found in a dichotomized description for fields with nodular tumors. The results support the concept that pretreatment hypothermic conditions can lead to an increase in thermal sensitization and may help explain the excellent clinical results noted in the treatment of superficial tumors with radiation and hyperthermia. Further exploitation of this approach by planned cooling of superficially-located recurrent tumors prior to hyperthermia treatment warrants investigation.

Comparison of intracervical, intrauterine, and intratubal techniques for donor insemination.

OBJECTIVE: To compare the efficacy of intracervical insemination (ICI), intrauterine insemination (IUI), and a combination of intratubal and intrauterine insemination (ITI/IUI) for donor insemination. DESIGN: Prospective randomized clinical trial. SETTING: The University of Michigan donor insemination program. PATIENTS, PARTICIPANTS: Forty-one women undergoing donor insemination with cryopreserved sperm for either isolated male factor or male factor plus ovulatory dysfunction corrected by clomiphene citrate. INTERVENTION: Each patient was randomly assigned to receive each of the three insemination techniques in consecutive cycles until pregnancy occurred or the patient dropped from the study. MAIN OUTCOME MEASURES: Cycle fecundity rates were compared using the chi 2 test, and cumulative pregnancy rates (PRs) determined by life table analysis were compared using a log-rank test. RESULTS: Cycle fecundity rate was significantly higher for IUI (18.3%) than for ICI (3.9%) or ITI/IUI (7.3%). By life table analysis, the cumulative PR for IUI was significantly higher than for ICI, but the PR for ITI/IUI was not. CONCLUSION: For donor insemination with cryopreserved sperm, IUI increases cycle fecundity compared with ICI. The addition of ITI to IUI, however, interferes with the apparent beneficial effect of IUI alone.

Greatly improved recovery of in vitro B-memory cell function after enzymic dispersion of immunized mouse spleens.

We have used the protease dispase to disperse the fine clumps that persist after mechanical disruption of spleens from immunized mice. After 4-8 days in culture, the resulting 'D/C' cells spontaneously generated many more IgG plaque-forming cells (PFC) against sheep erythrocytes (SRBC) than did conventional (CONV) suspensions. The difference averaged 12-fold and was consistently high after a wide range of immunization protocols. The major difference between the two cell preparations proved to be in the B-cell lineage rather than in antigen-presenting cells or T cells and, indeed, the response was largely T-cell independent. Antigen-driven culture responses to SRBC were also more than 10-fold higher with D/C than with CONV suspensions, and again there was apparently an improved recovery of B-memory cells. However, when fresh cell preparations were assayed immediately for PFC, there was no D/C:CONV difference--just as we have previously reported for memory responses on cell transfer to irradiated recipients. One simple interpretation is that germinal centres tend to remain as fine clumps on mechanical disruption, and their constituent B-memory cells are enriched by our procedure. If so, their responses are much more evident in vitro than after cell transfer.

Initial and steady state pharmacokinetics of cilazapril in congestive cardiac failure.

Twenty one patients with NYHA class II-III congestive heart failure received single ascending doses of 0.5, 1.25 and 2.5 mg cilazapril daily followed by the minimum effective dose for six weeks. Fifteen patients completed the study, but the data from only 11 were sufficiently complete for kinetic evaluation. The pharmacokinetics of the metabolite, cilazaprilat, after a single dose of 0.5 mg cilazapril were similar to previous observations in healthy volunteers at identical dosage. Repeat administration, however, led to greater accumulation than previously observed in volunteers at the higher dosages of 1.25 or 5 mg given for 8 days. Seven patients experienced adverse events. Four were severe, leading to withdrawal of the patients from the study, but only one event was related to cilazapril. Of the other three, one suffered a myocardial infarction and subsequently died due to worsening congestive heart failure. One other patient was withdrawn with two adverse events probably related to cilazapril. No other deaths occurred amongst the study population, and there were no significant abnormalities in haematology or blood chemistry.