Piperacillin/tazobactam compared with cefuroxime/ metronidazole in the treatment of intra-abdominal infections.

OBJECTIVE: To assess the effect of piperacillin/tazobactam compared with cefuroxime/metronidazole in the treatment of patients with intra-abdominal infections. DESIGN: Randomised open study. SETTING: 16 Swedish and 6 Norwegian hospitals. SUBJECTS: 269 patients with intra-abdominal infections were randomised and treated with at least one dose of each study drug. 205 patients, 105 treated with piperacillin/tazobactam and 100 with cefuroxime, were clinically evaluable for follow up (had been given the full course of treatment). INTERVENTION: Patients were given piperacillin 4g/tazobactam 0.5 g every 8 hours or cefuroxime 1.5 g every 8 hours plus metronidazole 1.5 g every 24 hours. Each patient was to be treated for a minimum of 3 days and not more than 10 days. MAIN OUTCOME MEASURES: Clinical evaluation of infection at the end of and 4-6 weeks after treatment. Evaluation of safety and tolerance to the drugs and bacteriological susceptibility to the treatment drugs. RESULTS: In the intention to treat analysis treatment was equally successful for piperacillin/ tazobactam (103/140, 74%) and the cefuroxime/metronidazole groups (90/129, 70%) (p = 0.6). Corresponding figures for the clinically evaluable group were 102/105 (97%) and 94/100 (94%) for piperacillin/tazobactam and cefuroxime/metronidazole groups, respectively, at the end of treatment. At late follow up, 92/105 (88%) and 83/100 (83%) in the two groups, respectively, remained free of infection. The side effects of the treatment were mild and evenly distributed between the two groups. Most pathogens were susceptible to the drugs in both treatment groups. CONCLUSION: Both piperacillin/tazobactam and cefuroxime/metronidazole are well suited to the treatment of patients with intra-abdominal infections, and we found no significant difference between the two. The drugs were safe and well tolerated in the regimens used.

Effects of oophorectomy on interstitial fluid pressure, blood flow and vascularity in a rat mammary tumour.

Interstitial fluid pressure (IFP), tumour size, blood flow and vascularity were measured in dimethyl-benz-alpha-anthracene-induced rat mammary tumours after oophorectomy. IFP was measured in the tumours by the wick-in-needle technique, blood flow by the labelled microsphere technique and vascularity by fluorescence vascular staining. Tumour volume was determined by measuring two diameters. Oophorectomy resulted in a decrease in tumour volume preceded by a decrease in IFP, while no significant change was observed in total tumour blood flow. The vascular cross-sectional area seemed to decrease. Cell proliferation may be of importance for the high interstitial fluid pressure in this hormone dependent tumour. A reduced metabolic requirement in the regressing tissue, down-regulating the vascular capacity, may camouflage the influence of the reduced tissue pressure on blood perfusion.

Perfusion characteristics and norepinephrine reactivity of human renal carcinoma.

Kidneys, surgically removed due to carcinoma, were subjected to perfusion in vitro. The perfusion distribution was studied by means of labeled microspheres injected during maximal vascular dilation and during two different norepinephrine concentrations. The perfusion concluded with injection of barium sulfate. Two-mm-thick slices of tissue were autoradiographed and microangiographed for visualization of perfusion and distribution of vascular density, respectively. Multiple specimens from tumor and cortical tissues were subjected to quantitative perfusate flow analysis. In spite of regionally high vascular density, perfusion through "normal-sized" capillaries was very low in tumor tissue as compared to cortex (during maximal dilation, one-tenth of the cortical flow). During moderate norepinephrine infusion, the perfusate flow decreased, and the resistance of the cortex increased. The flow to tumor tissue increased while the vascular resistance remained constant. During higher norepinephrine concentrations, the flow was redistributed; i.e., the cortical flow increased while that of the tumor decreased, due to a marked increase in tumor vascular resistance while the cortical tissue showed a very moderate rise in resistance. The thin-walled tumor vessels might be collapsed under a high tissue pressure at low perfusion pressures. At higher perfusion pressure, the vessels might open up, and contractile activity may not be expressed until then. The tumor vascular resistance increased 3 to 4 times, while that of cortex showed a 7-fold increase. Indications that a considerable fraction of the perfusate passes arteriovenous passages larger than 15 micron were obtained in individual experiments, this fraction increasing upon norepinephrine infusion.

Vascular reactivity to norepinephrine of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors and normal tissue as studied in vitro.

Vascular reactivity to norepinephrine has been studied in dimethyl-benz(a)anthracene-induced rat mammary neoplasia and compared with that of skeletal muscle, salivary gland, kidney, and uterus by means of an artificial perfusion technique. Perfusion of tissues and organs was measured with the microsphere tracer technique during smooth muscle relaxation and infusion of norepinephrine at two different dose levels. This procedure makes possible a dose-response analysis of several tissues under controlled conditions without confounding endogenous vasoregulation. The tumor vascular bed has a low perfusion capacity during smooth muscle relaxation and responds rapidly with an increased resistance to norepinephrine infusion. The results indicate a hypersensitivity, although the relative maximal constrictor response is equal to or less than that of other vascular beds studied.

Effects of noradrenaline on interstitial fluid pressure in induced rat mammary tumours.

Interstitial fluid pressure was measured by the wick-in-needle technique in DMBA-induced rat mammary tumours during resting conditions and during noradrenaline infusion. The rate of infusion was chosen to increase the systemic blood pressure by 30-40 mmHg, known to result in a markedly increased vascular resistance of these tumours. During resting conditions tumour interstitial fluid pressure was 10.3 +/- 1.3 mmHg (n = 13) but fell to 7.0 +/- 1.1 mmHg (n = 13) during noradrenaline infusion. The results suggests that noradrenaline is likely to affect the pre-capillary resistance vessels of the tumour vascular bed. This result, together with earlier perfusion studies, indicates that noradrenaline is unsuitable for increasing tumour cell perfusion as an adjunctive in radiation and cytotoxic drug therapy.

Vascular resistance characteristics of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors and normal tissues as studied in vitro.

Vascular perfusion characteristics have been studied in dimethylbenz(a)anthracene-induced rat mammary neoplasia and compared with those of skin, skeletal muscle, salivary gland, kidney, spleen, uterus, and brain by means of an artificial perfusion technique. Perfusion of tissues and organs was measured by the microsphere tracer technique. This procedure makes possible a detailed hemodynamic analysis of several tissues under controlled conditions, in this study maximum vascular relaxation, without confounding endogenous vasoregulation. The maximal perfusion capacity, i.e., during smooth muscle relaxation, of tumors and various tissues was related to perfusion pressure at three levels by means of three differently labeled microspheres. Tumors, especially large ones, have a low maximum perfusion capacity, i.e., high vascular resistance, compared to most other tissues. For the tumors, a relatively high perfusion pressure is required to open up the otherwise collapsed vascular network.

Blood flow and reactivity to noradrenaline in induced and autotransplanted DMBA rat mammary neoplasia.

Blood flow during the 'resting condition' and during noradrenaline infusion was compared by means of a microsphere tracer technique in induced DMBA-tumours along the mammary ridge and in autotransplanted tumours, as well as in abdominal skin, skeletal muscle, liver and kidneys. During 'resting conditions' the blood flow of tumours transplanted into skeletal muscle of the hindlimb, liver and kidney was similar to that of the non-transplanted tumours present along the mammary ridges. A pronounced decrease of blood flow upon moderate noradrenaline infusion was characteristic of autotransplanted as well as non-transplanted tumours, which contrasted to the insignificant reaction of skeletal muscle. The striking similarities in blood flow and reactivity of non-transplanted DMBA tumours and autotransplanted ones, and the dissimilarities of the transplanted tumours and the hosting tissues, favour the idea that these tumours regulate their blood supply irrespective of host tissue.

Posttraumatic and postoperative acute acalculous cholecystitis.

Acute acalculous cholecystitis has been described following surgery unrelated to the biliary tract and after multiple trauma (DuPriest et al., 1979; Gately & Thomas, 1983; Herlin et al., 1982; Howard, 1981; Long et al., 1978; Orlando et al., 1983). Mortality rate is high, probably in part reflecting delayed diagnosis and treatment, since symptoms and signs of the primary disease often mask the symptoms of cholecystitis. Increased awareness of this rare condition might lead to more accurate diagnosis and treatment and thereby improved outcome. In this report three patients who developed acute acalculous cholecystitis following unrelated surgery or multitrauma are described.

Vascular reactivity and perfusion characteristics in 7,12-dimethylbenz(a)anthracene-induced rat mammary neoplasia.

Blood flow during "resting conditions" and during noradrenaline infusion were studied by the labeled microsphere technique in dimethylbenz(a)anthracene-induced mammary tumors, skin, muscle, and lung in the rat. Intratumoral distribution of flow was studied by autoradiography of spheres trapped in the vascular beds of the tumors. Histological examination was performed and correlated to the blood flow data. Mean blood flow to the tumors during "resting conditions" was relatively high (49 ml/min/100 g tissue) but was substantially decreased (5 ml/min/100 g tissue) during noradrenaline infusion which produced a pressure elevation of 35 mm Hg. Thus, vascular resistance of the tumor tissue increased dramatically. Cardiac output increased, but total systemic resistance was unchanged. Vascular resistance in muscle was unchanged in contrast to an increase seen in skin. Shunted systemic blood flow to the lungs and bronchial arterial flow decreased indicating reactivity of abnormally large arteriovenous passages in the tumors. Poorly differentiated tumors had a higher vascular resistance than did well-differentiated tumors. Autoradiography revealed a nodular flow distribution with a slight tendency of higher perfusion in the periphery of these tumors.

Interstitial fluid pressure in DMBA-induced rat mammary tumours.

Interstitial fluid pressure (IFP) in DMBA-induced rat mammary tumours was measured by micropuncture with sharpened glass capillaries (diameter 1-3 micron) and by the 'wick-in-needle' technique (WIN). IFP in the superficial layers of the tumours (depth less than 800 micron) was measured with micropuncture, while WIN was used for measurements in deeper areas. IFP in the superficial layers of the tumours was 2.4 mmHg (SD 2.4, n=19), while IFP in deeper layers increased with increasing tumour weight. Thus central IFP in tumours weighing more than 5.5 g was 16.0 mmHg (SD 4.8, n=10), with a maximum value of 23.3 mmHg. When related to tumour histopathology a significant correlation was found between high cellular differentiation (i.e. low degree of malignancy) and high interstitial fluid pressure only. The high IFP may be secondary to a high capillary protein premeability and/or a relatively insufficient lymphatic drainage. A further rise in IFP might result from ischaemic cell swelling and/or a continuous cell proliferation within a tissue of rather low compliance. Together or alone one or more of these factors could facilitate the development of a compartment syndrome with concomitant cell death and tissue necrosis.

Percutaneous drainage of intraabdominal fluid collections.

Nine cases of percutaneous drainage of intraabdominal fluid collections in eight patients are reported. Ultrasonography and conventional radiography was utilized to make the diagnosis and to plan and perform puncture and drainage. In one case of subhepatic abscess only punction and aspiration was performed. In all other cases draining catheters were left between 3 and 21 days. Except in one case which later proved to be a cystic adenopapillary carcinoma of the kidney the results were good.