APACHE II score and abdominal sepsis. A prospective study

Therapeutic trials for intra-abdominal sepsis require pretreatment stratification; physiologic scoring has been recently proposed for this purpose. We have prospectively tested the validity of one such scoring system, namely, the Acute Physiology and Chronic Health Evaluation (APACHE II). As part of a larger database, we correlated APACHE II scores with mortality in 100 patients hospitalized for generalized peritonitis or abdominal abscess. Use of steroids was recorded because of our suspicion that steroids increase mortality but blunt the physiologic response to sepsis. Thirty-one patients died, including 12 of 19 patients receiving steroids. Stepwise discriminant analysis revealed that the APACHE II score and steroid use were each independently associated with the rate of mortality. We report a prospective validation of pretreatment APACHE II scoring in abdominal sepsis. Steroid use is an independent risk factor.     

Multimodality treatment of locally advanced breast carcinoma

Forty patients with 41 locally advanced breast lesions at stages IIIA and IIIB and the inflammatory stage were treated with combined-modality therapy from July 1980 to August 1985. Treatment included induction chemotherapy consisting of three cycles of fluorouracil, doxorubicin hydrochloride, and cyclophosphamide, followed by mastectomy in those patients whose lesions were operable (n = 28), and resumption of chemotherapy. Nine patients received postoperative radiation therapy. The mean follow-up was 34 months. Greater than 50% reduction in tumor size was achieved in 72% of patients after three cycles of chemotherapy. Overall, local control was achieved in 85% of patients with 59% survival and 53% disease-free survival, while 10% of patients developed local recurrences. Excluding lymphedema of the upper extremity (n = 2) and inflammatory carcinomas (n = 4), local control was achieved in 96% of patients, with 75% survival and 68% disease-free survival, while 4% of patients developed local recurrences. The rate of disease-free survival was 71% in patients with partial response to chemotherapy, contrasted with 43% in patients who did not respond or only minimally responded to chemotherapy. Actuarial five-year survival, based on life-table analysis, was calculated to be 46% for the group overall, 58% for the group excluding lymphedema of the upper extremity and inflammatory carcinoma, and 56% for the 28 patients undergoing mastectomy.     

Regional differences in cardiovascular risk factor profile cannot fully explain differences in cardiovascular morbidity in the Netherlands: a comparison of two urban areas

BACKGROUND: Our objective was to investigate whether a region in the south of the Netherlands (Heerlen/Kerkrade) had a high burden of cardiovascular disease in comparison with a nearby region (Maastricht) and the average Dutch population, respectively. We also wanted to determine if there are interregional differences in cardiovascular risk factor profile. DESIGN: Cross-sectional study. METHODS: Data from a nationwide registry (CBS) were used to analyse cardiovascular mortality in the two regions and the average in the Netherlands. Data from a primary care morbidity registration network (RNH) were used to compare cardiovascular morbidity and cardiovascular risk factors in both regions. A standardisation procedure was carried out for age and sex. Data were analysed using logistic regression analyses. RESULTS: The overall cardiovascular mortality rate was higher in the Heerlen/Kerkrade region (7.8 per thousand) compared with Maastricht (6.1 per thousand, OR=1.3, 95% CI 1.2-1.5) and the average in the Netherlands (5.7 per thousand). Similarly, most cardiovascular morbidity rates for Heerlen/Kerkrade were more elevated compared with the RNH overall and with Maastricht. Prevalence rates of risk factors such as diabetes mellitus (7.2%, OR=1.5, 95% CI 1.3-1.7) and overweight (10.8%, OR= 2.0, 95% CI 1.8-2.2) were significantly higher in the Heerlen/Kerkrade region compared with Maastricht. There were no differences with regard to hypertension (15.2%, OR=1.0, 95% CI 0.9-1.1). CONCLUSION: Heerlen/Kerkrade is indeed a region with a high burden of cardiovascular disease. Differences in morbidity between Heerlen/Kerkrade and Maastricht cannot be fully explained by differences in cardiovascular risk factor profile.     

Maturational gonadotropin from the African catfish, Clarias gariepinus: purification, characterization, localization, and biological activity.

A gonadotropic hormone of the African catfish, Clarias gariepinus, was was purified and chemically characterized. Its biological activity was tested and its localization in the gonadotropic cells of the pituitary demonstrated. An ethanolic extract of 500 pituitaries of adult male and female African catfish was subjected to ion-exchange chromatography on DE-52. The 31- to 38-kDa fraction was further purified on Sephadex G-75. On rpHPLC over an ODS 120T column two major components appeared as single bands after SDS-PAGE. From the amino acid composition and sequence analysis of these fractions, compared with those of salmon and carp GTH II-alpha and salmon GTH II-beta it was concluded that they represent catfish GTH alpha- and II-beta-subunits. The biological activity of the complete hormone (the 31- to 38-kDa fraction from the G-75 column) was tested on the production of 11 beta-hydroxyandrostenedione and 17 alpha-hydroxy-20 beta-dihydroprogesterone by catfish testis in vitro. Polyclonal antibodies were raised against the purified beta-subunit. Immunocytochemical study using these showed them to bind specifically to hypophysial gonadotropic cells. To date only one form of GTH has been demonstrated in the African catfish.     

Ligation of the intersphincteric fistula tract in low transsphincteric fistulae: a new technique to avoid fistulotomy

Aim To date fistulotomy is still the treatment of choice for patients with a transsphincteric fistula passing through the lower third of the external anal sphincter, because it is a simple, effective and safe procedure with a minimal risk of incontinence. However, data suggest that the risk of impaired continence following division of the lower third of the external anal sphincter is not insignificant, especially in female patients with an anterior fistula and patients with diminished anal sphincter function. It has been shown that ligation of the intersphincteric fistula tract (LIFT) is a promising sphincter‐preserving technique. Therefore, we questioned whether LIFT could replace fistulotomy in patients with a low transsphincteric fistula. Method A consecutive series of 22 patients with a low transsphincteric fistula of cryptoglandular origin underwent LIFT. Continence scores were determined using the Rockwood Fecal Incontinence Severity Index. Results Median follow‐up was 19.5 months. Primary healing was observed in 18 (82%) patients. In the four patients without primary healing, the transsphincteric fistula was converted into an intersphincteric fistula. These patients underwent subsequent fistulotomy with preservation of the external anal sphincter. The overall healing rate was 100%. Six months after surgery, the median incontinence score was not changed significantly. Conclusion Low transsphincteric fistulae can be treated successfully by LIFT, without affecting faecal continence. Division of the lower part of the external anal sphincter is no longer necessary in the treatment of low transsphincteric fistulae, which is essential for patients with compromised anal sphincters.     

Does pretreatment testing for serotonin transporter polymorphisms lead to earlier effects of drug treatment in patients with major depression? A decision-analytic model

BACKGROUND: An estimated 30% to 40% of patients with depression do not sufficiently respond to treatment with selective serotonin reuptake inhibitors (SSRIs) and the period in which treatment efficacy can be assessed is relatively long. Therefore, a test to identify potential nonresponders could be useful in the treatment of depression. Serotonin transporter gene (SLC6A4) variations have been reported to account for differences in the way individuals respond to SSRI treatment. OBJECTIVE: A decision-analytic model was used to assess whether pretreatment genetic testing for 5-HTTLPR, a polymorphism of the SLC6A4 genotype, could be an efficient tool in the treatment of depression. METHODS: A theoretical clinical decision-analytic model was constructed to compare the current treatment strategy in The Netherlands with an alternative strategy for the treatment of depression. Under treatment guidelines in The Netherlands, all patients with depression receive SSRI treatment (nontesting strategy). Under the alternative strategy, genetic testing would be performed to identify which class of antidepressant would be the best choice for initiation of treatment (genetic testing strategy). Probabilities (predicted results) for this model were based on data from previous studies and the opinions of experts in the field of psychopharmacology. To test the robustness of the model, 6- and 12-week remission rates for patients treated with SSRIs were varied in a sensitivity analysis using a predetermined range that was established based on expert opinion. Threshold analyses were performed on the parameters of serotonin transporter genotype frequency and response and nonresponse rates for patients receiving SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) to determine the value for a variable at which it could be concluded that a change in treatment strategy would be preferred. RESULTS: When genetic testing was performed before an antidepressant was prescribed, 64.6% of patients were predicted to be in remission after 6 weeks of treatment compared with 60.0% of patients who did not receive genetic testing. After 12 weeks, 79.5% of patients in the testing group who received an SNRI as initial treatment and 83.2% of those who received a TCA initially were predicted to be in remission compared with 76.7% of patients in the nontesting group. Sensitivity analyses indicated that the model was robust to variation of probability estimates within their plausible ranges. However, these findings were based on a theoretic model and did not include cost assessment. Pretreatment genetic testing must be evaluated further in randomized clinical trials and costs must be assessed before implementing this strategy in routine psychiatric practice can be recommended. CONCLUSIONS: The findings of this study suggest that performing genetic testing before prescribing antidepressant treatment may lead to greater numbers of patients experiencing remission early in treatment.     

Pouchitis: result of microbial imbalance?

To elucidate the role of microbiological factors in pouchitis, this study investigated the composition of ileal reservoir microflora, the mucus degrading capacity of bacterial enzymes as well as the pH and the proteolytic activity of pouch effluent. Stool samples were collected from five patients with pouchitis and nine patients without pouchitis. The flora of patients with pouchitis had an increased number of aerobes, a decreased ratio anaerobes to aerobes, less bifidobacteria and anaerobic lactobacilli, more Clostridium perfringens, and several species that were not found in control patients (for example, fungi). Furthermore the pH was significantly higher in patients with pouchitis (median value 6.5) than in control patients (5.4). To find out if the pH might influence the breakdown of intestinal mucus glycoproteins, the activity of glycosidases and proteases, and the degradation of hog gastric mucin by the pouch flora was tested at pH 5.2-7.6. Some glycosidases were inhibited, others were stimulated by a low pH, however, in each sample the proteolytic activity was inhibited for 75% at pH 5.2 compared with pH 6.8 and 7.6. Degradation of hog gastric mucin by the pouch flora was an active process at pH 7.2: within two to four hours of incubation more than half of the mucin was degraded. At pH 5.2 it took twice as long. It is concluded that pouchitis possibly results from instability of the flora in the pouch, which causes homeostasis to disappear (dysbiosis), and the protection of the pouch epithelium by the mucus layer becomes affected by increased activity of bacterial and host derived enzymes.