Small bowel perforation: is urgent surgery necessary?

BACKGROUND: Controversies regarding how urgent bowel perforation should be diagnosed and treated exist in recent reports. The approach for early diagnosis is also debatable. The purposes of this study were to evaluate the relationship between treatment delay and outcome of small bowel perforation after blunt abdominal trauma and to determine the best assessment plan for the diagnosis of this injury. METHODS: One hundred eleven consecutive patients with small bowel perforations caused by blunt abdominal trauma were retrospectively reviewed. The patients were divided into four groups according to the time interval between injury and surgery. Hospital stay, time to resume oral intake, and mortality and morbidity rates were compared between groups. Physical signs, laboratory and computed tomographic findings, and the results of diagnostic peritoneal lavage were analyzed to find the most sensitive and specific test for early diagnosis of small bowel perforation. RESULTS: Delay in surgery for more than 24 hours did not significantly increase the mortality with modern method of treatment; however, complications increased dramatically. Hospital stay and time to resume oral intake increased significantly when surgery was delayed for more than 24 hours. Abdominal tenderness was a common finding, but it was not specific for bowel perforation. Only 40% of the computed tomographic scans were diagnostic for bowel perforations: 50% of them showed suggestive signs, and 10% were considered as negative. Persistence of abdominal signs indicated peritoneal lavage. By using cell count ratio in diagnostic peritoneal lavage and/or increased lavage amylase activity, presence of particulate matter and/or bacteria in the lavage fluid, all patients with intraperitoneal bowel perforation were diagnosed accurately before operation. CONCLUSION: Small bowel perforation has low mortality and complication rates if it is treated earlier than 24 hours after injury. The principle of "rushing to the operation suite" for a stable blunt abdominal trauma patients without detailed systemic examination is not justified. The priority of treatment for the small bowel perforation should be lower than the limb-threatening injuries. Diagnostic peritoneal lavage provides high sensitivity and specificity rates for the diagnosis of small bowel perforation if a specially designed positive criterion is applied.     

腹膜外结肠造口一期乳头成形术的临床效果

目的探讨腹膜外结肠造口加一期乳头成形术的临床效果。②方法对５１例肛管和直肠癌病人施行腹膜外结肠造口一期乳头成形术,并与施行传统Ｍｉｌｅｓ腹膜内结肠造口术４０例病人的效果进行比较,观察造口并发症和排便功能改善情况。③结果５１例腹膜外结肠造口术病人经１～５年的随访,仅有１例发生造口旁疝,并发症的发生率为１．９％,４０例病人获排便感。对照组各种并发症的发生率为３０．０％,无１例病人有排便感。两组比较差异有极显著性（χ２＝１３．８０,Ｐ＜０．００１）。④结论腹膜外结肠造口一期乳头成形术具有并发症少,排便功能好,易于术后管理等优点。     

Immunohistochemical and ultrastructural analysis of dysplastic epithelium of human ocular surface: basement membrane and intermediate filament.

PURPOSE: The dysplastic corneal epithelium is characterized by the abnormal proliferation of epithelial cells. The phenotypes of these cells have not been elucidated. We investigated whether such epithelium expresses the phenotypes of corneal or conjunctival epithelial cells. METHODS: The corneas and conjunctivae from four normal subjects and from one patient with epithelial dysplasia of the central cornea were immunostained for IV and VII collagens and for cytokeratins. Monoclonal antibodies against collagen IV reacted to the [alpha1(IV)]2alpha2(IV) or alpha5(IV) molecule. Anti-cytokeratin antibodies were used to define epithelial cell types. The ultrastructure of the basement membrane (BM) of each specimen also was examined. RESULTS: Type VII collagen immunoreactivity was detected in all the specimens of epithelial BM. The anti-collagen IV [alpha1(IV)]2alpha2(IV) antibody labeled the conjunctival BMs, not the BMs of the corneal epithelia, of each subject. The normal corneal epithelial BM, not the BM of the conjunctival or dysplastic corneal epithelium, was immunolabeled with anti-alpha5(IV) antibody. The pattern of cytokeratin expression in the corneal epithelial dysplasia resembled that seen in the normal conjunctivae. Small breaks in the BM of dysplastic corneal epithelium were ultrastructurally revealed. The number of hemidesmosomes in the dysplastic corneal epithelium was decreased as compared with that in the normal BM. CONCLUSION: The composition of collagen types within the BM and the cellular phenotype of the dysplastic epithelium in the cornea resembled those of conjunctival epithelium, not of the cornea.     

Sequence-dependent antagonism between fluorouracil and paclitaxel in human breast cancer cells.

The effects of 24-hr exposures to 5-fluorouracil (FUra) and paclitaxel in various sequences were studied in MCF-7 breast cancer cells to determine an optimal schedule for possible clinical use. In clonogenic assays, pre-exposure to FUra followed by paclitaxel resulted in marked antagonism, while sequential paclitaxel followed by FUra was optimal. Concurrent or pre-exposure to paclitaxel did not affect [3H]FUra metabolism, [3H]FUra-RNA incorporation, or the extent of FUra-mediated thymidylate synthase inhibition. Paclitaxel led to G2/M phase accumulation that persisted for up to 24 hr after drug exposure, while a 24-hr FUra exposure produced S-phase accumulation. FUra pre-exposure diminished paclitaxel-associated G2/M phase block, whereas subsequent exposure to FUra after paclitaxel did not. FUra exposure resulted in transient induction of p53 and p21, which returned to basal levels 24 hr after drug removal. p53 and p21 protein content also increased markedly during paclitaxel exposure, accompanied by phosphorylation of Bcl-2. Double-stranded DNA fragmentation (approximately 50 kb) was seen at 48 hr when cells were exposed to paclitaxel for an initial 24-hr period. Paclitaxel-associated DNA fragmentation was not prevented by concurrent or subsequent exposure to FUra. Thus, paclitaxel-mediated G2/M phase arrest appeared to be a crucial step in induction of DNA fragmentation. Since an initial 24-hr paclitaxel exposure did not interfere with subsequent FUra metabolism or thymidylate synthase inhibition, and delayed exposure to FUra did not impede either paclitaxel-mediated induction of mitotic blockade or DNA fragmentation, the sequence of paclitaxel followed by FUra is recommended for clinical trials.     

CAMPATH-1H IN RHEUMATOID ARTHRITIS--AN INTRAVENOUS DOSE-RANGING STUDY

Forty-one patients with active and refractory rheumatoid arthritis(RA) received a total of 100, 250 or 400 mg of CAMPATH-1H (CAMPATHis a trademark of Glaxo-Wellcome group companies, registeredin the US Patent and Trademark Office) over 5 or 10 days inan open, uncontrolled study. Following therapy, patients weremonitored for adverse effects and disease activity for 6 months.Therapy was associated with prolonged peripheral blood lymphopeniain all dosing cohorts. During the month immediately followingtherapy, lymphopenia was most profound in the 400 mg cohorts.The first dose of monoclonal antibody (Mab) was associated witha ‘flu’-like syndrome, more pronounced at higherinitial doses. One patient developed haemolytic-uraemic syndrome.There were a number of dose-related infections during the earlypost-treatment period and one fatal opportunistic infectionwhich followed additional immunosuppressive therapy. Antiglobulinresponses developed in 9 of 31 patients tested. The majorityof patients showed symptomatic improvement following therapyand 20% of patients maintained a 50% Paulus response at 6 months,all of whom were in the 250 or 400 mg cohorts. CAMPATH- 1H appearsto be an effective treatment for RA. Allowing for the smallnumber of patients treated, infections were more common withhigher doses, although this was not true for adverse eventsoverall, and therapeutic responses were more sustained at higherdosing levels. The broad specificity of CAMPATH- 1H may be appropriatefor the immunotherapy of RA and future studies should aim todefine a dose with an optimal therapeutic ratio. KEY WORDS: CAMPATH-1H, Rheumatoid arthritis, Immunotherapy, Monoclonal antibody, Antiglobulin response     

The reversal of profound mivacurium-induced neuromuscular blockade

Purpose

Mivacurium is metabolized by plasma cholinesterase catalyzed ester hydrolysis. Acetylcholinesterase antagonists used in the reversal of muscle relaxation may also inhibit plasma cholinesterase and, therefore, delay the hydrolysis of mivacurium. The clinical interaction between acetylcholinesterase antagonists and mivacurium induced neuromuscular blockade was studied.

Method

Intraoperative muscle relaxation was maintained with a mivacurium infusion to achieve a constant intense block (first twitch, T¹, 2–3% of control). Patients were randomly divided into three groups. Patients in Group 1 received no anticholinesterase, in Group 2 neostigmine 0.07 mg · kg^?1, and in Group 3 edrophonium 1 mg · kg^?1. The times between termination of the mivacurium infusion (Group 1) or the administration of the anticholinesterase (Groups 2 and 3) to 25%, 50%, 75% and 95% T₁ recovery, and to 50%, 70% and 90% recovery in the ratio, T₄/T₁ (TR) were recorded.

Result

In the neostigmine Group, T₁ recovery to 25%, 50% and 75% ( 2.32 ± 1.41, 3.90 ± 1.85 and 6.88 ± 2.66 min) was accelerated compared with control (3.36 ± 1.34, 5.78 ± 2.22, and 8.58 ± 3.60, and), but recovery to 95% (18.53 ± 9.09 vs 13.29 ± 5.24 min) was delayed. Also, TR recovery to 50%, 70%, and 90% was slower (14.47 ± 8.73, 21.25 ± 11.06 and 31.37 ± 12.11 min vs 11.75 ± 3.74, 13.78 ± 4.39 and 17.86 ± 6.44 min). However, all T₁ and TR recovery times were decreased in the edrophonium group (0.88 ± 0.51, 2.00 ± 1.50, 4.97 ± 2.96, and 9.35 ± 5.24 min for T₁ and 6.86 ± 3.93, 9.05 ± 4.51 and 12.24 ± 6.66 min for TR).

Conclusion

Neostigmine reversal of intense mivacurium neuromuscular block should be avoided, as this may result in prolongation of the block.     

Accuracy of a rapid 10-minute carbon-14 urea breath test for the diagnosis of Helicobacter pylori-associated peptic ulcer disease

Urease in the human gastric mucosa is a marker for infection with Helicobacter pylori (HP), an organism which is associated with peptic ulcer disease. To detect gastric urease, we examined 184 patients (144 males, 40 females; mean age: 49.8±15.6 years) with suspected peptic ulcer disease. Fasting patients were given orally 5 Ci of carbon-14 labelled urea. From each patient only one breath sample was collected in hyamine at 10 min. The amount of ¹⁴C collected at 10 min was expressed as follows: [(DPM/mmol CO₂ collected)/(DPM administered)] × 100 × body weight (kg). The presence of HP colonization was determined by examination of multiple endoscopic prepyloric antral biopsy specimens subjected to culture or a rapid urease test. For the purpose of this study, HP-positive patients were defined as those with characteristic bacteria as indicated by a positive result of either the culture or the rapid urease test; HP-negative patients were defined as those with negative findings on both the culture and the rapid urease test. Of the 184 cases, 99 (53.8%) were positive for HP infection, and 85 (46.2%), negative. The sensitivity and specificity of the rapid 10 min ¹⁴C-urea breath test for the diagnosis of HP-associated peptic ulcer disease were evaluated by a receiver operating characteristic (ROC) curve with a variable cut-off value from 1.5 to 4.5. When a cut-off value of 1.5 was selected, the sensitivity was 100% and the specificity, 83.5%; when a cut-off value of 4.5 was selected, the sensitivity was 54.5% and the specificity, 97.6%. Correspondence to: Chia-Hung Kao     

Time course of satisfaction of search

"Satisfaction of search" (SOS) refers to the effect in which a second lesion remains undetected after detection of another lesion on the same radiograph. The objective of this study was to clarify our understanding of SOS by relating it to total time of inspection and time intervals before, between, and after discovery of lesions. Detection accuracy of native lesions in chest radiographs, before and after the addition of a simulated nodular lesion, was measured for ten observers. Analysis of data from this and a previous experiment showed that average perceptual accuracy of individual receiver operating characteristic curves was significantly reduced with the addition of the nodules. Plots and analyses of search time revealed that, on average, during a typical 46-second inspection of a case, simulated nodules were found at 18 seconds, native abnormalities at 25 seconds, and false positives occurred at 33 seconds. Time needed to find nodules did not depend on whether native lesions were present; time to find native lesions did not change with addition of nodules; and total search time was the same for images with one, two, or no lesions. The detection results show that the SOS effect was obtained, but that interrupting search in order to measure it also diminishes accuracy. Analysis of the time course data relates SOS to perceptual capture and strategic halting of search.     

Dopamine distribution and behavioral alterations resulting from dopamine infusion into the brain of the lesioned rat

In an effort to verify the "dopamine secretion hypothesis" as the mechanism responsible for the antiparkinsonian efficacy of adrenal medullary transplants into the brain, the effects of dopamine infusion into the brains of rats with unilateral substantia nigra lesions were examined. The apomorphine-induced rotation, characteristic of this animal model, was diminished after 7 days of continuous dopamine infusion (10 micrograms/hr) into the ipsilateral striatum, whereas intraventricular infusion was without effect. Chromatographic analysis of the dopamine distribution after 10 days of infusion into either region revealed that ipsilateral delivery of dopamine did not result in contralateral increases in dopamine content. Examination of the adjacent striatum following ipsilateral intraventricular delivery indicated that dopamine had only penetrated 1 mm. Even with intrastriatal delivery, there were still parts of the infused striatum which had below-normal levels of dopamine. The fact that striatal tissue presents a significant barrier to the penetration of dopamine is discussed in relation to adrenal medullary and fetal nigral transplants.     

The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.

Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.