Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy.

Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.

Visualization of data.

Data visualization has developed in several directions: theoretical; methodological; and in new application areas. Advances include the development of a grammar of graphics, deeper understanding of human perception and implications for graphical layout, and better approaches to visualizing multi-dimensional data and large data sets. Gene expression is a notable new application area for visualization of large data sets.

Pyomyositis in a patient with the acquired immunodeficiency syndrome.

Pyomyositis is an acute bacterial infection of skeletal muscle. It is a common disease in the tropics; fewer than 50 cases of pyomyositis have been reported in the continental United States. Most patients are healthy males, although the disease has been reported in diabetics and in the immunocompromised. This article presents the first detailed known reported case of pyomyositis in a patient with the acquired immunodeficiency syndrome; Staphylococcus aureus was the etiologic agent.

Influenza surveillance in an acute-care hospital.

The epidemiology, significance, and clinical consequences of influenza in the hospital setting were studied in a prospective surveillance of adults in an acute-care hospital during the 1986-1987 influenza season, specifically searching for cases of nosocomial influenza. A total of 43 cases of influenza A were identified; 17 cases occurred among working hospital employees, 14 cases occurred among patients in the emergency room or clinics, ten were community-acquired cases among hospitalized patients, and two cases were nosocomially acquired. The nosocomial influenza attack rate was 0.3 per 100 hospital admissions. Both cases of nosocomial influenza were associated with secondary pneumonias and prolongation of hospital stay. These cases might have gone unrecognized in the absence of an influenza surveillance program. A potential reservoir of infection was the health care providers caring for the hospitalized patients. Further systematic influenza surveillance is needed to assess the global medical and economic impact of nosocomial influenza on hospitals, rather than simply relying on reports of institutional outbreaks.

Coccidioidal meningitis. An analysis of thirty-one cases and review of the literature.

Clinical and laboratory features of 31 patients with coccidioidal meningitis seen from January 1964 through December 1976 with follow-up through 1979 are reported and data on 114 patients from the literature reviewed. History of exposure to C. immitis, a wide age range, and, in about one third, underlying conditions are noteworthy. Dissemination to the meninges usually occurs within the first few months although diagnosis is frequently delayed. Presenting symptoms and signs of coccidioidal meningitis are varied but signs of chronic meningitis or suggestion of hydrocephalus are prominent. Evidence of acute infection is unusual even with widespread disease. Diagnosis is usually made by demonstration of coccidioidal CF antibodies in the CSF although they are not found in all patients. Some show other direct evidence of C. immitis. Special diagnostic techniques such as CAT scanning for evidence of basilar meningitis or hydrocephalus are valuable. Amphotericin B remains the drug of choice despite the need for long-term therapy and the problems with intrathecal administration. Reservoirs are only occasionally useful but shunts are frequently lifesaving despite complications. Factors associated with a bad prognosis are hydrocephalus, non-Caucasian race, or presence of an underlying disease.

Legionnaires' disease: report of sixty-five nosocomially acquired cases of review of the literature.

Sixty-five cases of nosocomially acquired Legionnaires' disease are reported and the world literature is reviewed. The etiologic agent, Legionnella pneumophila, has been isolated from several environmental sources at outbreak sites. Legionnaires' disease appears to be acquired by inhalation and is primarily manifested by severe, potentially fatal, pneumonia. Characteristic clinical disease consists of high fever with relative bradycardia, dry cough, chills, diarrhea, and pleuritic pain. Although no single feature is pathognomonic, the clinical presentation is usually sufficiently characteristic to suggest the diagnosis. The diagnosis of Legionnaires' disease during acute illness may be established by culture of Legionella pneumophila, or by demonstration of the bacterium using special stains. However, in most instances, the physician must make a presumptive diagnosis based on the clinical presentation in order to institute appropriate antimicrobial therapy. Retrospective confirmation of the diagnosis may be made by serologic studies in most instances. Erythromycin is, at this time, the drug of choice for the treatment of Legionnaires' disease. A prompt salutory response following institution of erythromycin therapy is typical.

Fungal sinusitis in patients with AIDS: report of 4 cases and review of the literature.

We report here 3 cases of aspergillus sinusitis in patients with AIDS and the 1st fully described case, to our knowledge, of sinusitis associated with Pseudallescheria boydii in a patient with AIDS. We review the microbiology and pathology of fungal sinusitis in patients with AIDS and the morphologic and clinical features and treatment of P. boydii infection and aspergillus sinusitis. Fungal sinusitis in patients with HIV or AIDS generally occurs later in the course of primary disease with low CD4+ lymphocyte counts (< 50/mm3), unlike bacterial sinusitis which may occur at any time. Differentiation between invasive and noninvasive forms is likely not important, in contrast to fungal sinusitis in noncompromised patients. The number of cases is likely to increase as the number of patients with AIDS increases, patients survive longer, and other opportunistic infections are prevented or treated. Causative agents are likely to be resistant to fluconazole, which is in widespread use. Aspergillus sinusitis in patients with HIV or AIDS occurs in both those with and without traditional risk factors. Fungal sinusitis may present vexing management problems and be relentlessly progressive in the face of therapy. Ideal therapy has yet to be defined but an early combined surgical and medical approach in these compromised patients is preferred.

Risk factors and comparisons of clinical nephrotoxicity of aminoglycosides.

Controversy continues regarding risk factors for nephrotoxicity and the possible differences in nephrotoxicity rates associated with the aminoglycosides commonly used in clinical practice. Review of published data, including 27 comparative clinical studies, indicates the following: sensitive markers of tubular toxicity do not correlate directly with clinically significant diminution in glomerular filtration rate; of all the proposed risk factors, few are consistently found; despite numerous studies, some with potential drawbacks, no current aminoglycoside has been shown to be consistently and conclusively less nephrotoxic than another; and, as per a previous recommendation, the choice of an aminoglycoside should not be made on the basis of nephrologic criteria.

Symposium on infectious complications of neoplastic disease (Part II). Legionnaires' disease. Aspects of nosocomial infection.

Tremendous progress has been made recently in characterization of Legionella pneumophila and infections caused by it. Certain areas that are particularly germane to immunosuppressed patients, who are affected more frequently than other patients, and areas that are controversial and merit particular consideration are considered herein. These include pathogenesis and correlation of experimental and clinical evidence, nosocomial outbreaks and almost ubiquitous distribution of L. pneumophila in water despite only a limited number of studies linking the two by aerosols, prevalence and possible reasons for the apparent spotty distribution, protean clinical manifestations, difficulties in diagnosis, certain aspects of therapy, and control by environmental changes.

Amikacin therapy for gram-negative septicemia.

Amikacin was administered to 18 patients with gram-negative septicemia. Ten of the patients had blood culture isolates highly resistant to gentamicin; six of these patients had persistent bacteremia while receiving gentamicin alone or in combination with other agents. Fourteen of the 18 patients were cured with amikacin therapy and adjunctive measures. Nine of the 10 patients with gentamicin-resistant pathogens were cured. The occurrence of nephrotoxicity in four patients with elevated amikacin serum levels and serious underlying disease indicates the desirability of monitoring serum amikacin levels. Minor ototoxicity occurred in two patients and was associated with prolonged therapy and high serum amikacin levels. Amikacin is a highly effective agent for treating patients with gram-negative bacteremia; it is the agent of choice in the therapy of patients with suspected or documented gram-negative bacteremia caused by pathogens resistant to gentamicin and susceptible to amikacin.

Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections.

The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms.

Radiographic features of Legionnaires' disease.

Serial chest radiographs of 35 patients with confirmed Legionnaires' disease were evaluated. A unilateral, unilobar alveolar infiltrate was, in general, the initial radiographic finding. Progression to consolidation or to new areas of involvement was typical. Every lobe was involved, but lower lobe involvement was most common. Pleural effusion was often present. Cavitation was not seen. Radiographic progression for several days following institution of therapy, and despite clinical response, was noted. In patients who survived, radiographic improvement of abnormalities was usually apparent within two weeks of therapy. Aradiographic spectrum exists and, although many features are typical, no single feature is pathognomonic.

Miconazole for treatment of disseminated coccidioidomycosis. Unfavorable experience.

Miconazole at dosages up to 30 mg/kg/day was given intravenously to seven patients with complicated courses of disseminated coccidioidomycosis. Six had received treatment with amphotericin B previously and five of these patients could be evaluated for the efficacy of the treatment. In three patients the condition failed to respond to therapy, another patient required intratracheal administration of amphotericin B later, and the fifth patient had an equivocal response to treatment. Severe phlebitis, pruritus, nausea, vomiting, hyperlipidemia, and thrombocytosis were frequent side effects. These limited unfavorable results indicate that until controlled studies demonstrate its safety and efficacy, therapy with miconazole should be reserved for highly selected patients with disseminated coccidioidomycosis who cannot receive amphotericin B.

Identification of low-risk hospitalized patients with pneumonia. Implications for early conversion to oral antimicrobial therapy.

PURPOSE: Few available data exist to define either the medically necessary duration of parenteral antimicrobial therapy or length of stay for hospitalized patients with pneumonia. Therefore, we investigated the potential safety and effectiveness of a practice guideline recommending early conversion of low-risk patients with pneumonia from parenteral to oral antimicrobial therapy and early hospital discharge. PATIENTS AND METHODS: The practice guideline was studied retrospectively in 503 hospitalized patients with pneumonia at a teaching community hospital. RESULTS: Thirty-three percent of patients with pneumonia were classified as at low risk for complications and potentially suitable for early conversion to oral antimicrobial therapy according to the guideline. Were the guideline to have been used to guide patient discharge decisions, 619 additional bed-days would have been made available to accommodate incoming patients. A consensus among physician reviewers led to the judgment that quality of care would not have worsened for 98.2 percent of low-risk patients had they been switched to oral antimicrobial therapy on the third hospital day, nor would quality of care have been worsened for 93.4 percent of low-risk patients had they been discharged on the fourth hospital day. CONCLUSION: The practice guideline that we studied has the potential to safely reduce the duration of parenteral antimicrobial therapy and length of hospital stay for selected low-risk patients with pneumonia. The guideline should be studied in a prospective clinical trial.

Group G streptococcal endocarditis.

The group G streptococcus may be a more common human pathogen than previously recognized. A case of group G streptococcal endocarditis is reported and the 11 cases reported previously are reviewed. Group G endocarditis may have significant clinical and prognostic differences from endocarditis caused by the more commonly identified viridans or group D streptococci. Routine serologic grouping of beta-hemolytic streptococcal isolates from serious infections is warranted.

Regulation of oligodendrocyte development and central nervous system myelination by insulin-like growth factors.

In summary, our studies show that IGFs are potent regulators of oligodendrocyte development and myelination in vitro and in vivo. IGFs act at several levels: by promoting proliferation of oligodendrocytes and oligodendrocyte precursors, by inducing immature oligodendrocyte precursors to develop into oligodendrocytes, and by regulating myelin gene expression and the amount of myelin produced per oligodendrocyte. Our findings indicate that IGFs play a crucial role in normal oligodendrocyte development and myelination, and suggest that IGFs may have applications for the promotion of remyelination in myelin disorders such as MS.

Legionella infections.

Legionnaires' disease is a distinct clinical entity caused by Legionella pneumophila. Following an epidemic of pneumonia in Philadelphia in 1976, it was found that the bacterium had in fact been first isolated in 1947. Other species of Legionella have been identified, many of which are indistinguishable from L. pneumophila infection. Legionella species also cause extrapulmonary infections and a mild nonpneumonic form of disease known in its epidemic form as Pontiac Fever.

Imported echinococcosis in southern California.

A retrospective chart review conducted at two teaching hospitals in Los Angeles County identified 28 patients with infection due to Echinococcus granulosus diagnosed by positive echinococcal serology and/or tissue biopsy between January 1981 and December 1990. Of these patients, 25 (89%) were foreign born and 19 (68%) were immigrants from the Middle East or central Asia. Only 12 of 22 immigrants questioned about epidemiologic risk factors described a history of rural residence or direct exposure to dogs in their native country. Single cysts of liver, lung, and soft tissue were present in six of 28 patients; multiple cysts in the 22 remaining patients were exclusively hepatic in 13 patients, exclusively pulmonary in two patients, and involved mixed sites including liver, lung, abdomen, central nervous system, and bone in seven patients. Natives of middle eastern countries currently constitute a major risk group for imported infection due to E. granulosus in the United States. Since their epidemiologic risk factors may be absent and clinical presentations varied, a high index of suspicion for echinococcosis is warranted in this population based solely on the presence of a cystic mass in liver, lung, or another organ site.

In vitro synergy studies with ciprofloxacin and selected beta-lactam agents and aminoglycosides against multidrug-resistant Pseudomonas aeruginosa.

In order to determine the effect of combining ciprofloxacin with beta-lactam and aminoglycoside agents against multidrug-resistant P. aeruginosa, ciprofloxacin was tested in vitro with the checkerboard broth microdilution technique with various current beta-lactam and aminoglycoside agents. In both inhibitory and bactericidal testing, the combination of ciprofloxacin with a beta-lactam agent (ceftazidime, piperacillin, mezlocillin, azlocillin, or imipenem) was more likely to show a synergistic effect or additive effect and lack of antagonism (96.5% of all inhibitory and cidal tests) than was a combination of ciprofloxacin with an aminoglycoside [(amikacin, tobramycin, or gentamicin), 90% of all inhibitory and cidal tests]. Finding of antagonism in some testing, especially with aminoglycosides, indicates that results are unpredictable. These results may influence selection of agents for selection in clinical situations.

Determination of the effect of antimicrobics in combination against Listeria monocytogenes.

The in vitro activity of selected penicillins, extended spectrum cephalosporins, vancomycin, gentamicin, erythromycin, tetracycline, rifampin, and trimethoprim and sulfamethoxazole (alone and in combination) was determined by microtiter technique for 20 isolates of Listeria monocytogenes. The activity of selected combinations of antimicrobics was determined by the microtiter checkboard technique. Trimethoprim-sulfamethoxazole (1:20 ratio) was the most active agent in inhibitory tests and also showed bactericidal activity. The combinations of gentamicin with either ampicillin or vancomycin and that of erythromycin with tetracycline showed bactericidal effect in synergy studies. Combining ampicillin with an extended spectrum cephalosporin showed no antagonism, whereas, combining rifampin with trimethoprim or with trimethoprim/sulfamethoxazole led only to indifference or antagonism. These observations may have importance in selection of therapy in animal models or in selected clinical situations.