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This paper aims at presenting a new approach to the management of uncertain lumpy demand. After providing a comprehensive review of the related literature, a new approach is introduced here in order to reduce the need for stocks when coping with uncertain lumpy demand. The basic idea of this approach is that of exploiting available information within the company or within the company's supply chain, so as to minimize the impact of lumpy orders and reduce the need for stocks. Two theoretical models are presented here to address the trade-off between the benefit of the lower inventory level and the cost of the higher risk related to the anticipatory use of uncertain information: the first model treats the lumpy order quantity as deterministic, while the arrival of the order is considered as a stochastic event; the second model deals with the opposite situation, when the arrival of a lumpy order is certain, while the order quantity is uncertain. These new models turn out to have a relevant interpretative power, and seem useful in real-life management of lumpy demand, since they can boost running capital productivity resorting to information usually available within or around the company, although often not exploited.

Aims and background Carcinoma of the colon-rectum is an infrequent cause of brain metastases, constituting 1-5% of all metastatic lesions to the brain. We reviewed our experience in the treatment of brain metastases from colorectal cancer to define the efficacy of whole brain radiation therapy as a palliative measure in this setting of patients.Methods Twenty-three consecutive cases of brain metastasis from colorectal cancer treated between 1999 and 2004 were identified in the files of the Division of Radiotherapy of the A Businco Regional Oncological Hospital, Cagliari. Their records were reviewed for patient and tumor characteristics and categorized according to the RTOG RPA classes.Results Fifteen patients (65%) had multiple metastases. Twenty-one patients (91%) showed extracranial metastases. Fourteen patients were classified as RTOG RPA class II and 9 class III. The median radiation dose delivered was 2000 cGy in 5 fractions in one week (range, 20-36 Gy). In 14 of 20 assessable patients (70%), symptomatic improvement was observed. The median follow-up and survival time for all the patients, 12 females and 11 males, was 3 months. In 3 patients only the cause of death was the brain metastasis.Conclusions Despite the disappointing survival time, external radiation therapy to the whole brain proved to be an efficacious palliative treatment for patients with multiple or inoperable brain metastasis from colorectal cancer.

Platelet-mediated antibacterial activity against gram-negative microorganisms has been investigated. Data show that human washed platelets possess the ability to partially inhibit growth ofSalmonella typhi Ty-2 (a smooth strain) but not of two rough strains ofSalmonella minnesota (R345-Rb and R595-Re). On the other hand, no antibacterial activity was noted in the presence of the gram-positiveStaphylococcus aureus. This activity is dependent on the length of incubation of platelets with bacteria and apparently is not mediated by platelet soluble factors. Finally, lysis of platelets with Triton X-100 following their incubation with bacteria gives rise to the same degree of antibacterial activity observed in the untreated samples. This implies that the described platelet function does not rely on the possible trapping of bacteria in platelet aggregates.

Summary We investigated thein vitro effect of various members of the genusLegionella on human peripheral mononuclear cells. All the strains tested induced the generation of strong procoagulant activity (tissue factor) when incubated for a prolonged period of time with pure mononuclear cell suspensions. This effect was dependent on the number of bacteria. The production of mononuclear cell procoagulant activity was also observed after the addition of bacteria to citrated whole blood.Escherichia coli 0111:B4 showed similar activity, butStaphylococcus aureus was much less effective. These findings suggest that the presence of endotoxin-like substance(s) in the outer cell wall ofLegionellae could contribute to the stimulation of mononuclear cells. The production of tissue factor, a potent trigger of blood clotting, by these cells could help us to understand the mechanism(s) responsible for the activation of intravascular coagulation associated with severe legionellosis.

High molecular weight kininogen (HK) is a multifunctional plasma glycoprotein that occupies a critical position in pathways that link inflammation and coagulation. Excision of the vasoactive peptide bradykinin by plasma kallikrein results in kinin-free HK that consists of a 65-Kd N-terminal heavy chain (HK-HC) linked to the C-terminal 45- Kd light chain (HK-LC) by a disulfide bridge. HK-HC is an inhibitor of SH-proteases and HK-LC contains the binding sites for coagulation cofactors prekallikrein and factor XI. HK has previously been shown to bind specifically to human umbilical vein endothelial cells (HUVEC) in a zinc(2+)-dependent manner by a single class of high-affinity binding sites. We have further characterized that interaction in order to determine the cell-binding regions of HK. Competition binding experiments have indicated that either HK-LC or HK-HC was able to inhibit the binding of labeled HK with a 50% inhibitory concentration (IC50) of 77 nmol/L and 89 nmol/L, respectively. Cleaved two-chain HK (HKa) had an IC50 of 73 nmol/L, whereas uncleaved HK had an IC50 of 335 nmol/L. Direct binding experiments have indicated that HUVEC bind both purified [125I]HK-HC and [125I]HK-LC in a zinc(2+)-dependent manner and that HK-LC did not displace bound HK-HC. The light chain of low molecular weight kininogen or prekallikrein-binding region of HK did not inhibit the binding of HK to HUVEC. Our results, therefore, indicate that (1) HK is capable of binding to endothelial cells via both heavy and light chain moieties, (2) HKa has a higher affinity to HUVEC, and (3) purified heavy and light chains are capable of directly binding to HUVEC. The data are consistent with the presence of a single high-affinity site for HK on endothelial cells within which are subsites that bind to heavy and light chains.

Thromboembolic complications are known in cancer patients after i.v. administration of Corynebacterium parvum. We examined the ability of this organism to induce production of procoagulant activity by human blood mononuclear leukocytes in vitro. After 4 hours incubation Corynebacterium parvum was an effective stimulant for mononuclear leukocytes, behaving in the same way as the typical gram‐negative bacterium Escherichia coli, whereas mononuclear cells incubated with Staphylococcus aureus were not affected. Corynebacterium parvum used was found devoid of endotoxin by the Limulus assay and was not affected by Polymyxin B, which, on the contrary, inhibited Escherichia coli‐induced production of procoagulant activity. Intact Corynebacterium parvum may be required for the production of procoagulant activity and, although this specific aspect of the research will require further study, from the exposed data it is concluded that such a production could be a factor contributing to the pathogenesis of the coagulopathy following Corynebacterium parvum therapy.

Blood clotting parameters were measured in six patients with gynecologic tumors following i.v. administration of acetic acid-treated Salmonella minnesota R595 (Re), which has been previously demonstrated to enhance impaired immune functions in the same patients. Although these bacteria possess a more exposed lipid A at their surface which has the potential to stimulate the coagulative cascade, no evidence of plasma hypercoagulative state was detected. In fact, procoagulant activity generated by patients' mononuclear cells after Salmonella treatment was not significantly higher than that produced by patients' cells before treatment. Moreover, other haemostatic laboratory parameters were unaffected by in vivo treatment with bacteria.

We studied platelet function and antithrombrin III levels in 30 insulin-dependent diabetic children with no clinically evident vascular complications. 9 were in-patients and 21 were out-patients. The disease had been discovered within the previous 10 years. 25 control subjects of comparable age and body weight were studied simultaneously. Template bleeding time, threshold concentrations of ADP or adrenaline required to induce irreversible platelet aggregation and plasma antiheparin activity (platelet factor 4) did not differ significantly in control and patient groups. In contrast, the immunological levels of plasma antithrombin III were significantly higher in the diabetic group. These results suggest that diabetic children, with no clinical signs of microangiopathy, show no laboratory changes suggesting increased platelet function. The unexpected increase in the antithrombin III level could reflect a very early defense mechanism against activation of the blood clotting system.

Objectives: Despite antibiotic prophylaxis for at-risk mothers during labour and delivery, Streptococcus agalactiae (group B Streptococcus; GBS) still causes substantial morbidity and mortality among newborns. In addition to the well-known side effects of the administration of antibiotics, resistance to drugs recommended for penicillin-allergic pregnant women, such as erythromycin and clindamycin, has increased, thus raising concern about the possibility of inadequate prophylaxis. On this basis we evaluated the antimicrobial activity of benzalkonium chloride against GBS, which has been described as an antimicrobial agent for the topical treatment of vaginal infections.Methods: A total of 52 GBS from pregnant women have been studied. The capacity of benzalkonium chloride as well as of penicillin, erythromycin, clindamycin, vancomycin, chloramphenicol and tetracycline to inhibit GBS was evaluated using broth macrodilution and microdilution methods, respectively.Results: While all the strains were penicillin- and vancomycin-susceptible, 19.2% were resistant to both erythromycin and clindamycin. In contrast, all GBS isolates were either inhibited or killed by benzalkonium chloride at not only low but also very similar concentrations (MIC90 = 3.12 mg/L).Conclusions: Benzalkonium chloride might represent an alternative strategy that is useful in reducing vaginal GBS colonization in pregnant women before delivery by topical treatment.

Lipoglycans from mycoplasmas possess the ability to induce the elaboration of procoagulant activity. This represents a third endotoxic property for these polymers, in addition to the pyrogenicity and clotting of Limulus lysate reported previously. Lipoglycans from three species of Acholeplasma (A. axanthum, A. granularum, and A. oculi) stimulated the elaboration in vitro of procoagulant activity by human mononuclear cells to differing extents. Two serotypes, 3 and 4, of Ureaplasma urealyticum also exhibited this stimulatory activity. The activities of lipoglycans tested were, in decreasing order, A. oculi greater than U. urealyticum type 4 greater than A. axanthum greater than U. urealyticum type 3 greater than A. granularum.

The effects in vitro of 4 purified lipopolysaccharide (LPS) preparations from Rickettsiae on platelets and leucocytes were studied in rabbits and in man. All LPS induced aggregation in rabbit platelet-rich plasma but to differing degrees. This activity was abolished by inactivation of complement. None of the preparations induced aggregation of human platelets. Both rabbit and human leucocytes, when incubated with each of the rickettsial LPS preparations, generated a potent procoagulant activity (tissue factor). These findings add further support to the concept that rickettsial LPS behave as typical LPS from gram-negative bacteria and may be relevant to the understanding of the mechanism(s) responsible for triggering intravascular coagulation in rickettsial diseases.

In October 1990 pneumonia due toLegionella pneumophila was diagnosed in two employees working in the area of Apulia, southern Italy, where artesian wells were in construction. Although the exposure to excavation has been associated with Legionnaires' disease, in our investigation the illness occurred only in those employees who were present when the water emerged from the ground under high pressure. On the basis of this report, water appears as the most likely reservoir of the organism and the main route of infection.