Biomedical subjects

Baruch Brenner

Publications and source records attributed to Baruch Brenner.

At least 19 recordsLinked to original sources

PubMed2006

Small bowel obstruction caused by secondary tumors.

Small bowel obstruction in an oncology patient is a common and serious medical problem which is associated with diagnostic as well as therapeutic dilemmas. While the condition is most commonly caused by postoperative adhesions and peritoneal carcinomatosis, other causes have been reported [Cormier WJ, Gaffey TA, Welch JM, et al. Linitis plastica caused by metastatic lobular carcinoma of the breast. Mayo Clinical Proceedings 1980;55:747-53; Clavien P-A, Laffer U, Torhos J, et al. Gastrointestinal metastases as first clinical manifestation of the dissemination of a breast cancer. European Journal of Surgical Oncology 1990;16:121-6; Bender GN, Maglinte DD, McLarney JH, et al. Malignant melanoma: patterns of metastasis to the small bowel, reliability of imaging studies, and clinical relevance. American Journal of Gastroenterology 2001;96:2392-400; Gatsoulis N, Roukounakis N, Kafetzis I, et al. Small bowel intussusception due to metastatic malignant melanoma. A case report. Technical Coloproctology 2004;8:141-3; Hung GY, Chiou T, Hsieh YL, et al. Intestinal metastasis causing intussusception in a patient treated for osteosarcoma with history of multiple metastases: a case report. Japanese Journal of Clinical Oncology 2001;31(4):165-7; Chen TF, Eardley I, Doyle PT, Bullock KN. Rectal obstruction secondary to carcinoma of the prostate treated by transanal resection of the prostate. British Journal of Urology 1992;70(6):643-7; Kamal HS, Farah RE, Hamzi HA, et al. Unusual presentation of rectal adenocarcinoma. Roman Journal of Gastroenterology 2003;12(1):47-50; Hofflander R, Beckes D, Kapre S, et al. A case of jejunal intussusception with gastrointestinal bleeding caused by metastatic testicular germ cell cancer. Digestive Surgery 1999;16(5):439-40]. One of these, reported thus far in only very few patients, is obstruction caused by secondary tumors, i.e. metastases from other organs to the small bowel wall. As cancer patients live longer with improved therapy, physicians are more likely to cope with rare phenomena of neoplasms, such as small bowel obstruction caused by secondary tumors. We hereby present a review of the relevant medical literature. The goal of this article is to define current knowledge on this phenomenon, with emphasis on its epidemiology and clinical characteristics, and to increase the awareness of the clinician treating cancer patients of such possibility.

Female↗

PubMed2006

Preoperative chemoradiation in rectal cancer: Retrospective comparison between capecitabine and continuous infusion of 5-fluorouracil.

BACKGROUND: We compared the efficacy and toxicity of oral capecitabine and continuous infusion of 5-fluorouracil (5-FU) in the preoperative chemoradiation treatment of patients with rectal cancer. PATIENTS AND METHODS: The files of 89 patients with rectal cancer, 43 treated preoperatively with oral capecitabine and 46 with intravenous 5-FU, were reviewed, and the outcome of the groups was compared. RESULTS: There was no statistically significant difference in the complete pathological response rate between the capecitabine and the 5-FU groups (30% vs. 17%, P = 0.15). The downstaging rate was higher in the capecitabine group (77% vs. 50%, P = 0.009). Toxicity was mild in both groups. The rate of Grade 3 gastrointestinal toxicity was similar in the two groups (diarrhea 2% vs. 4%, proctitis 5% vs. 7%), except for one patient in the 5-FU group (2%) who developed a rectovaginal fistula. In the capecitabine group, one patient (2%) had Grade 3 hand-foot syndrome, and another had an acute myocardial infarction. In the 5-FU group, two patients (4%) had Grade 3 hematological toxicity, and three (6%) had complications from Port-a-Cath insertion. CONCLUSION: Preoperative chemoradiation with oral capecitabine appears to be safe and well tolerated, and at least as good as continuous 5-FU.

Administration, Oral↗

PubMed2005

A phase I clinical trial of the sequential combination of irinotecan followed by flavopiridol.

PURPOSE: Flavopiridol potently enhances the effect of irinotecan with cures in colorectal cancer xenografts, and is associated with modulation of several molecular targets, including p21, Differentiation-related gene 1 (Drg1), and p53. We initiated a phase I trial of the sequential combination of irinotecan followed by flavopiridol to determine the maximal tolerated dose of this combination therapy. PATIENTS AND METHODS: Forty-five patients with advanced solid tumors were enrolled. Irinotecan was administered first (100 or 125 mg/m(2)) followed 7 hours later by escalating flavopiridol (10-70 mg/m(2)) given weekly over 1 hour for 4 of 6 weeks. At the maximal tolerated dose, the pharmacokinetic analysis was expanded and pre- and posttreatment tumor biopsies were done. RESULTS: At irinotecan 100 mg/m(2), dose-limiting diarrhea and myelosuppression were observed with flavopiridol 70 mg/m(2). At irinotecan 125 mg/m(2), we observed dose-limiting hyperbilirubinemia, fatigue, and myelosuppression at flavopiridol 60 mg/m(2). Peak flavopiridol concentrations of >/=2 mumol/L were achieved above flavopiridol 50 mg/m(2). No significant pharmacokinetic interactions with irinotecan were noted. Baseline serum bilirubin significantly predicted cycle 1 dose-limiting toxicity and neutropenia. We observed partial responses in three patients and prolonged stable disease (i.e., >6 months) in 36% of patients including adrenocortical cancer and hepatocellular cancer. Patients with wild-type p53 and either no change or low posttreatment biopsy p21 and a decrease in Drg1 expression showed stable or responsive disease to the combination therapy. CONCLUSIONS: The recommended phase II dose with irinotecan 100 mg/m(2) is flavopiridol 60 mg/m(2) and with irinotecan 125 mg/m(2) is flavopiridol 50 mg/m(2). Toxicity can be predicted by baseline bilirubin. Clinical activity is encouraging and may correlate to changes in p21 and Drg1 levels in patients with wild type p53 tumors following therapy.

Adult↗

PubMed2005

Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma.

Colorectal carcinoma is one of the most common cancers in the world, and more than 50% of these patients develop liver metastases. Despite recent advances, systemic chemotherapy for metastatic disease without the use of surgery is considered palliative, as there are rarely long-term survivors. However, patients who are candidates for surgical resection of their liver metastases can have a prolonged survival or possibly a cure. Consensus guidelines on criteria for resection and prognostic scores help facilitate patient selection, yet only 25% of patients with liver metastases are considered to have resectable metastases. Neoadjuvant chemotherapy has been explored in an attempt to render more patients candidates for resection. First reports using neoadjuvant systemic chemotherapy in patients with unresectable disease found that 13% to 16% of patients could be rendered resectable. Efforts to increase response rates using hepatic arterial infusion or biologic agents may increase resection rates. This review summarizes the current data on neoadjuvant chemotherapy, the rationale for this approach, potential complications, and future prospects.

Antineoplastic Agents↗

PubMed2005

[Treatment approach to localized esophageal cancer--what have we learned so far?].

The treatment of localized esophageal cancer (LEC) is under extensive debate. Treatment approaches include surgery or radiation alone, surgery with preoperative or postoperative radiation, preoperative or postoperative chemotherapy and definitive or preoperative chemoradiation. In fact, the type of therapy patients receive is often dependent on the actual medical field of the treating physician (surgery, oncology, etc.). The use of multiple treatment approaches toward LEC primarily reflects the scarcity of data that is derived from controlled randomized trials and the poor results of current therapies. In spite of the above, the cumulative data suggest that surgery and chemoradiation are the two treatment options in LEC and that their combined approach, i.e. preoperative chemoradiation, has not been proven to have a survival advantage over each one of these methods, and should therefore still be considered investigational. This article will review the available data on the various treatment approaches that are being used against LEC.

Combined Modality Therapy↗

PubMed2004

Small-cell carcinomas of the gastrointestinal tract: a review.

PURPOSE: To improve our understanding of the entity of small-cell carcinoma (SmCC) of the gastrointestinal (GI) tract. METHODS: A MEDLINE search was done, using the terms "small cell carcinoma" or "oat cell carcinoma" combined with "gastrointestinal" or with any of the GI sites, for the period 1970 to 2003. The 138 eligible reports identified in this way were reviewed for clinical data. RESULTS: To date, approximately 544 cases of GI SmCC have been reported. The disease represents 0.1% to 1% of all GI malignancies, with the esophagus being the most common primary site. A majority of patients present with overt distant metastases. Systemic symptoms are common; ectopic hormonal secretion may occur. By light microscopy, GI SmCCs are essentially indistinguishable from primary pulmonary SmCC. The presence of non-SmCC components is common. Data from molecular analysis of the disease has identified some similarities to pulmonary SmCC. Chemotherapy represents the main treatment option, with modest impact on survival. In locoregional disease, the literature suggests that treatment be initiated using chemoradiotherapy and then, if metastatic disease is still excluded, surgical resection be considered. The disease is highly aggressive, and survival is in the range of several weeks for untreated patients and of 6 to 12 months for those receiving therapy. CONCLUSION: SmCC of the GI tract is a rare and lethal disease. Although there are many similarities to pulmonary SmCC, some differences between the two entities are suggested. While chemotherapy can achieve significant palliation, surgery may have a potential impact on long-term survival of patients with locoregional disease.

Adolescent↗

PubMed2004

Phase I trial of combined-modality therapy for localized esophageal cancer: escalating doses of continuous-infusion paclitaxel with cisplatin and concurrent radiation therapy.

PURPOSE: To define the maximum-tolerated dose (MTD) of paclitaxel when given as a weekly 96-hour infusion with cisplatin and radiotherapy for patients with esophageal cancer. PATIENTS AND METHODS: Thirty-four patients with locally advanced esophageal cancer and three patients with local recurrence or positive resection margins were treated. Weekly paclitaxel doses of 10, 20, 30, 40, 60, and 80 mg/m(2), given as a continuous 96-hour infusion, were administered with weekly cisplatin, 30 mg/m(2) on day 1, weeks 1 to 6, and concurrent radiation (50.4 Gy). Plasma paclitaxel steady-state levels were measured. RESULTS: Dose-limiting toxicity, defined as a treatment break longer than 2 weeks for toxicity, occurred in one patient in the 80-mg/m(2)/wk dose level. Major causes for any (including < or = 2 weeks) treatment breaks were mediport complications and neutropenic fever, which occurred mostly at that dose level. At a paclitaxel dose of 60 mg/m(2)/wk, myelosuppression, mostly neutropenia, was relatively mild and transient; stomatitis, esophagitis, diarrhea. and peripheral neuropathy were uncommon and usually of grade 2 or less. Therefore, the MTD was established at 60 mg/m(2)/wk. The mean steady-state concentration of paclitaxel at the MTD was 17.2 nmol/L. Complete (R0) resection was possible in 16 (73%) of 22 patients who underwent subsequent surgery, and the pathologic complete response rate was 24%. CONCLUSION: Weekly, 96-hour infusion of paclitaxel 60 mg/m(2)/wk, given with concurrent cisplatin and radiotherapy, is a safe and tolerable regimen for patients with localized esophageal cancer. Preliminary efficacy data are encouraging. This regimen is the basis of ongoing Radiation Therapy Oncology Group phase II randomized trials in esophageal and gastric cancers.

Adult↗

PubMed2004

Is the delay in starting postoperative radiotherapy a key factor in the outcome of advanced (T3 and T4) laryngeal cancer?

OBJECTIVE: To identify factors influencing the outcome of postoperative radiotherapy in patients with advanced laryngeal cancer. DESIGN: The files of 44 patients with advanced laryngeal cancer who were treated by surgery followed by radiotherapy (24 with pT3 and 20 with pT4) were reviewed. Median delay in starting radiotherapy was 50 days (range, 19-150 days). Treatment variables, in addition to certain patient and tumor characteristics, were analyzed in terms of locoregional control and survival. SETTING: Major referral tertiary center in central Israel. RESULTS: Locoregional control rates were 86% and 81% at 2 and 5 years, respectively, and corresponding survival rates were 82% for both. Only nodal involvement retained statistical significance for both locoregional control as well as survival on multivariate analysis (P = 0.0009 and P = 0.0004, respectively). CONCLUSIONS: This is the first study showing that delay in postoperative radiotherapy in advanced laryngeal cancer is not a significant predictor of locoregional control or survival in advanced laryngeal cancer. Only lymphatic spread was found to have a significant influence on treatment outcome.

Adult↗

PubMed2004

Treatment of localized esophageal cancer.

The treatment of localized esophageal cancer (LEC) is controversial. The approaches that are used in daily practice include surgery or radiation alone, preoperative or postoperative radiation, preoperative or postoperative chemotherapy, and definitive or preoperative chemoradiation. The varied modalities used to treat LEC reflect both the lack of randomized trial data and the suboptimal results with current therapy. Nonetheless, the available data suggest that surgery and definitive concurrent chemoradiation represent two standard treatment options. The use of preoperative chemoradiation remains investigational, with phase III trials failing to demonstrate a consistent benefit for this option over chemoradiation or surgery alone. This review will examine the available data on the current treatment approaches in LEC.

Combined Modality Therapy↗

PubMed2004

c-kit expression in primary and metastatic merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin that is associated with a high incidence of recurrence and metastasis. The therapeutic arsenal for this malignancy is limited and once it spreads, there is no effective treatment. c-kit expression has been demonstrated previously in primary MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit expressing tumors. In this study we examine 25 additional primary MCCs and also 6 of their lymph node metastases. Formalin-fixed, paraffin-embedded tissues were stained immunohistochemically with an antibody directed against the KIT receptor. Percentage and intensity of staining were analyzed semiquantitatively using a three-tiered system. Twenty-one of the 25 (84%) primary tumors stained positively for KIT, of which 14 (67%) showed widespread positivity. Five of the 6 lymph nodes (83%) were similarly positive. High mitotic rate and vascular invasion in the primary tumors tended to be associated with prominent staining in the lymph node metastases. No association was found between c-kit expression and outcome. We confirm that the majority of primary MCCs express c-kit and further find that metastases are positive for the KIT receptor as well. Thus, c-kit expression may be an early event in the transformation of MCC, but not a marker for tumor progression.

Aged↗

PubMed2003

Patterns of failure in patients with malignant melanoma treated with high-dose interferon-alpha2b in the adjuvant setting.

The aim of this prospective study was to record the pattern of failure associated with high-dose interferon-alpha2b (IFN) adjuvant therapy after surgery. It included 55 consecutive patients with stage IIB and III melanoma (median age 50 years) rendered disease-free by surgery but considered at high risk for relapse from a tertiary referral, university-affiliated medical centre. Intervention consisted of IFN 20 mU/m(2) per day intravenously, 5 days a week for 4 weeks, followed by subcutaneous IFN 10 mU/m(2) per day three times a week for 48 weeks. Treatment was stopped at completion of protocol, at disease progression or due to unacceptable toxicity. Dose modification followed treatment-related toxicity. Twenty-six of the 55 patients (47%) relapsed: 14 during treatment and 12 after completion of the protocol. Eighteen of these 26 patients (69%) relapsed initially in a single organ, most commonly in soft tissue or the CNS. A single metastasis was noted in 12 of the 18 patients, and multiple metastases confined to a single organ were detected in the other six. No statistically significant survival advantage could be demonstrated in association with any of the patterns of relapse. Patients treated for stage IIB disease fared better than those treated for stage III disease, regardless of whether the regional metastases were microscopic or palpable. IFN seems to be more commonly associated with a single-organ/single-metastasis pattern of failure, and more soft tissue and CNS relapses. This pattern did not translate into a survival advantage in this series. Larger databases should be explored to validate these trends.

Adolescent↗

PubMed2003

High dose rate brachytherapy for nonmalignant airway obstruction: new treatment option.

STUDY OBJECTIVES: High dose rate (HDR) endobronchial brachytherapy is widely used as a palliative treatment for symptomatic airway obstruction by primary or secondary malignant tumors. We report on a successful use of HDR brachytherapy in patients with nonmalignant airway obstruction. DESIGN: Case series PATIENTS: Six patients received HDR brachytherapy for airway obstruction caused by granulation tissue around a metal stent placed for restoration of the airway patency for nonmalignant causes. In four patients, brachytherapy was performed following recurrent occlusion of the airway by granulation tissue formation; in two patients, it was done as a prophylactic procedure. INTERVENTION: HDR brachytherapy catheters were passed through the metal stents under direct fluoroscopic guidance. Simulation and computerized treatment planning were done, and a single dose of 10 Gy was administered using a brachytherapy remote afterloader with a (192)Ir source. The dose was prescribed to a distance of 1 cm from the center of the source, with a margin of 1 cm from the proximal and distal ends of the stent. RESULTS: At a median follow-up of 15 months, moderate granulation tissue formation was observed in only one patient; in four others, it was categorized as minimal, 5 to 30 months from the procedure. Restoration of the lumen was complete in four patients, near complete in one patient, and partial in one patient. In one patient, previously treated by external radiotherapy, local tissue necrosis was evident. CONCLUSION: HDR brachytherapy can be used safely for nonmalignant airway obstruction. Further studies including more patients and longer follow-up are needed.

Adult↗

PubMed2002

Classical Kaposi sarcoma: prognostic factor analysis of 248 patients.

BACKGROUND: Classical Kaposi sarcoma (CKS) is a rare indolent neoplasm that is particularly prevalent among Jews of Ashkenazi and Mediterranean origin. Data regarding prognostic factors for CKS are scarce. The aim of the current retrospective analysis was to better define prognostic subgroups among patients with CKS. METHODS: Between 1960 and 1995, 248 consecutive patients with CKS were treated at the Rambam and Rabin Medical Centers in Israel. Although treatment options included local excision, radiotherapy, and chemotherapy, observation alone was used for 31% of patients. For prognostic factor analysis, disease progression was classified as any progression and dissemination, and progression-free survival was calculated for each. RESULTS: At a median follow-up of 20 months, four patients (1.6%) died of CKS. Of the patients eligible for analysis, 94 of 220 (39%) had any progression and 23 of 120 (18%) had dissemination. Only 8 of 202 (4%) had visceral spread. On univariate analysis, age was a statistically significant prognostic factor for any progression (P = 0.04), whereas immunosuppression and visceral involvement at presentation had only borderline significance. Immunosuppression was the only prognostic factor for dissemination (P = 0.003). On multivariate analysis, both age and immunosuppression were significant prognostic factors for any progression (P = 0.001 and 0.01, respectively). Immunosuppression was also predictive of dissemination (P = 0.006). CONCLUSIONS: Immunosuppression and older age (50 years and older) are strongly associated with poorer outcome among CKS patients. The two end points used in this study may be used for future prognostic factor analyses.

Adult↗

PubMed2002

Male breast carcinoma in Israel: higher incident but possibly prognosis in Ashkenazi Jews.

BACKGROUND: Little information is available regarding male breast carcinoma. However, cumulative data have suggested a propensity for the disease among Ashkenazi Jews. Because Ashkenazi Jews comprise one of the major ethnic groups in Israel, the authors conducted a local study to shed more light on the features of this rare disease. METHODS: From 1960 to 2000, 131 men with breast carcinoma were treated at the Rabin Medical Center or the Rambam Medical Center, and, from 1980 to 1997, 470 patients with this diagnosis were recorded in the Israel Cancer Registry. These two data bases were used to analyze the epidemiologic and clinicopathologic characteristics of male breast carcinoma in Israel. RESULTS: Seventy-eight percent of the 131 Jewish patients were Ashkenazi. Most of their clinical characteristics were similar to those of their Sephardic counterparts. However, there was a statistically significant difference in the pattern of comorbidity between these groups (P = 0.000), and there was a trend toward a younger age at onset and more advanced tumor stage at the time of diagnosis for the Sephardim. It also was found that Sephardic origin was associated with poorer outcome (P = 0.03). Analysis of the Cancer Registry data base revealed an 80% increase in the risk of the disease for Ashkenazi Jews compared with Sephardic Jews (odds ratio, 1.8; 95% confidence interval, 1.4-2.3; P = 0.001). Survival analysis from this source suggested a poorer outcome for Sephardic Jews compared with Ashkenazi Jews (62% vs. 64.3% estimated 5-year survival rates, respectively; P = 0.08). CONCLUSIONS: Analyses of two independent data bases, patient charts, and a cancer registry indicate that breast carcinoma seems to be more prevalent among Ashkenazi Jewish men. At the same time, affected Ashkenazi patients may have a more favorable outcome than their Sephardic counterparts.

Adenocarcinoma↗

PubMed2002

Characterization of novel breast carcinoma-associated BA46-derived peptides in HLA-A2.1/D(b)-beta2m transgenic mice.

The human milk fat globule membrane protein BA46 (lactadherin) is highly overexpressed in human breast tumors, making it a potential target for tumor immunotherapy. We have identified BA46-derived peptides that contain the motif recognized by the MHC class I molecule HLA-A2.1 and that are processed and presented by human breast carcinoma cells. In mice lacking normal class I molecules but expressing an HLA-A2.1/D(b)-beta2 microglobulin single chain (HHD mice), three peptides elicited specific CTL activity. Two of these peptides also stimulated cytotoxic activity in peripheral blood lymphocytes from HLA-A2.1-positive breast carcinoma patients. Adoptive transfer of HHD-derived bulk CTLs to nude mice bearing human breast carcinoma transplants reduced tumor growth. These peptides therefore represent naturally processed BA46-derived CTL epitopes that can be used in peptide-based antitumor vaccines.

Adoptive Transfer↗

PubMed2002

[Ricin--from a Bulgarian umbrella to an optional treatment of cancer].

Ricin toxin, found in the bean of the castor plant, is one of the most toxic and easily produced plant toxin. It is composed of two polypeptide chains linked by a disulfide bond. The toxin irreversibly blocks protein synthesis. Oral intoxication is the most frequent mode of exposure, but direct contact and inhalation have also been described. A single intramuscular exposure was reported, related to an assassination event in 1978. The clinical signs of intoxication begin hours after the exposure, and include gastrointestinal signs, dyspnea, fever, vasculatory collapse, neurological signs, liver necrosis and renal failure. Treatment is mainly supportive. A vaccine has been developed and found effective in animal studies. Ricin may be used as a biological weapon due to its heat stability and worldwide availability. A more friendly use, which has been tested in clinical trials, is the incorporation of ricin-immunotoxin for the treatment of cancer patients.

Bulgaria↗

PubMed2002

[Detection and identification of a biological attack].

It is difficult to detect bioterrorism attacks and to identify the castoff biological agent. The principal enigmas are the wide variety of the clinical symptoms associated with various biological agents and the fact that the attack is likely to be a covert event. The first and major indication of a bioterrorism attack could be the presence of affected patients. It is, however, extremely important to detect and identify an attack using a biological agent as early as possible. Therefore, it is crucial to be alert to such possibilities and to maintain high levels of suspicion. The aim of this article is to list all the clues, which will help us highlight the suspicion that a disease or clinical symptoms are the result of a bioterrorism attack and not a "natural" outbreak. These clues involve the recognition of a wide range of clinical patterns pertinent to biological agent attacks on the individual victim and the overall integrated epidemiological picture. Further signs also include the identification of the roots of transmission, the contagious patterns of bioterrorism agents and possible unusual findings in laboratory tests and in animals.

Bioterrorism↗

PubMed2002

[The spectrum of symptoms associated with biological warfare].

BACKGROUND: There are hundreds of potential agents that could be used in biological warfare or bioterrorism: bacteria, viruses and toxins. There are no similarities between clinical presentations of organisms or toxins belonging to specific microbial families. Therefore, it is important for the physician, required to cope with an unusual disease or outbreak among his patients, to become familiar with the various symptoms that victims of biological warfare or bioterrorism may present. METHODS: To describe the six most common groups of symptoms expected in the above setting. The most common symptoms will be described as they appear in nature, because of a fortunate lack of experience with the majority of these agents in biological warfare. Hence, variations of these presentations may be possible. RESULTS: The six most common presentations reviewed are: 1) respiratory tract symptoms; 2) hemorrhagic fevers; 3) meningitis and encephalitis; 4) flaccid paralyses; 5) fever syndromes with rash; and 6) diarrheal syndromes. Additional presentations may be possible due to alterations made in these organisms or development of new agents and mixtures. A list is provided of features that may alert a physician of the possibility of biological warfare or bioterrorism. CONCLUSION: Knowledge of the principal clinical presentations of victims of biological warfare or bioterrorism is essential to all physicians. This knowledge may contribute to the early recognition of a cluster of patients, an epidemic, an unusual disease, or biological warfare; quick referral to the emergency department, leading to early microbiological diagnosis; and rapid notification of the Ministry of Health. All these, and the institution of appropriate measures, will ultimately contribute to the survival of individual patients and at-risk populations.

Biological Warfare↗