An online Sexual Health and Rehabilitation eClinic (TrueNTH SHAReClinic) for prostate cancer patients: a feasibility study.

PURPOSE: The primary objective was to determine the feasibility of implementing the TrueNTH SHAReClinic as a pan-Canadian sexual health and rehabilitation intervention for patients treated for localized prostate cancer. METHODS: The feasibility study was designed to evaluate the accessibility and acceptability of the intervention. Participants from five institutions across Canada were enrolled to attend one pre-treatment and five follow-up online clinic visits over 1 year following their prostate cancer (PC) treatment. RESULTS: Sixty-five patients were enrolled in the intervention. Website analytics revealed that 71% completed the intervention in its entirety, including the educational modules, with an additional 10% completing more than half of the intervention. Five thousand eighty-three views of the educational modules were made along with 654 views of the health library items. Over 1500 messages were exchanged between participants and their sexual health coaches. At 12 months, the intervention received an overall average participant rating of 4.1 out of 5 on a single item satisfaction measure. CONCLUSION: Results support the TrueNTH SHAReClinic as highly acceptable to participants as defined by intervention adherence and engagement. The TrueNTH SHAReClinic demonstrated promise for being a feasible and potentially resource-efficient approach to effectively improving the sexual well-being of patients after PC treatment.

Corynebacterium parvum: immunomodulation in local bacterial infections.

Inoculation with Corynebacterium parvum 14 days before bacterial challenge produced protection against murine-simulated surgical wound infection with Escherichia coli to the same degree as had been provided by Bacillus Calmette-Guerin pretreatment. Simulated surgical wound infection induced by Staphylococcus aureus in mice followed a much more variable course; bacterial growth was depressed 7 days after C. parvum inoculation and was equivocal at a 14 day interval. Unlike E. coli infection modified by C. parvum or BCG, bacterial growth was significantly enhanced when the interval between C. parvum inoculation and S. aureus challenge was 20 or 28 days. Explanations for these differences and their possible clinical relevance are discussed.

Serum kinetics of intraperitoneal moxalactam.

Continuous intraperitoneal administration of antibiotics has been recommended as treatment for peritonitis. The necessity of simultaneous systemic administration of antibiotics remains undefined but usually is performed. Moxalactam kinetics in serum were studied in dogs receiving 15 mg/kg intravenously; 15 mg/kg intraperitoneally; 5 mg/kg hourly with peritoneal lavage; 15 mg/kg intravenously followed by 5 mg/kg hourly intraperitoneally; 15 mg/kg intraperitoneally after 24 hours of peritonitis; and 5 mg/kg hourly by peritoneal lavage after 24 hours of peritonitis. Intraperitoneally administered moxalactam resulted in sustained serum levels compared with intravenously administered drugs. Repeated exchanges in lavage fluid resulted in progressively higher serum levels with each exchange. Peritonitis results in statistically higher levels of serum antibiotic concentration when compared with controls. Continuous intraperitoneal lavage with antibiotics would not appear to require concomitant systemic drug therapy.

Nonspecific enhancement of resistance to local bacterial infection in starved mice.

We studied the effect of muramyl dipeptide (MDP) on enhancing resistance to local bacterial challenge in starved mice. The challenge consisted of the intramuscular insertion of a suture laden with Klebsiella pneumoniae. Mice that had been pretreated with MDP had a statistically lower rate of bacterial recovery at the site of the challenge, had consistently fewer bacteria in the blood, and had improved short-term survival. By enhancing local bacterial containment, MDP pretreatment of immunocompromised animals reduces the level of bacteremia and subsequent mortality.

Simulated surgical wound infection in mice: effect of stimulation on nonspecific host defense mechanisms.

Experiments were conducted to ascertain whether nonspecific host defenses could be enhanced in a reliable animal model simulating the local bacterial infection that frequently complicates surgical wounds. The test lesion was studied in detail and exemplifies the concept that the ultimate expression of the host-pathogen interaction is the capacity of that pathogen to persist or grow in a given host. Mice were challenged by intramuscular insertion of cotton suture impregnated with 10(7) to 10(8) Escherichia coli K-12. The mice were subsequently killed at intervals, and the suture and muscle mass were retrieved, homogenized, and quantitatively cultured. Numbers of viable organisms in tissue from control animals were compared with those from experimental animals that received BCG (Bacillus Calmette-Guérin) vaccine, a nonspecific immunostimulant, prior to bacterial challenge. Improved tissue antibacterial activity appeared in animals that had received BCG vaccine 13 days prior to bacterial challenge. Differing doses and intervals were not protective. Enhancement of nonspecific host defense mechanisms may be helpful in combination with current measures for improved control of surgical wound infection.

Treatment of pneumonia in mechanically ventilated trauma patients. Results of a prospective trial.

OBJECTIVES: To determine the efficacy and magnitude of associated adverse effects of 2 different antibiotic regimens for the treatment of pneumonia in intubated surgical patients and to assay and compare blood samples and bronchoalveolar lavage fluid with respect to some host-defense parameters, especially in patients with unilateral pneumonia. DESIGN: Randomized, prospective, unblinded clinical comparison of 2 treatment arms with respect to intent to treat and clinical and microbiologically evaluable patients. SETTING: Six university surgical services in teaching hospitals with modern and well-staffed intensive care units. INTERVENTIONS: The consistency and objectively of the diagnosis of pneumonia was improved by the use of a grid of diagnostic parameters. Aggressive mechanical approaches to pneumonia in intubated surgical patients were supplemented by therapeutic use of aztreonam and vancomycin hydrochloride or combined imipenem and cilastatin sodium. RESULTS: Patients randomized to the aztreonam-vancomycin group were somewhat more ill, fared slightly better, and had fewer serious drug-related side effects than did those treated with imipenem-cilastatin (all P > .05). Immunologic parameters assessed by evaluation of bronchoalveolar lavage fluid showed differences between infected pulmonary lobes and noninfected ones; some changes were also noted in patients who recovered compared with those whose pneumonia persisted or recurred. CONCLUSIONS: Clinical studies of pneumonia in surgical patients need to be stratified to assure comparability, to identify patients in whom treatment is likely to fail, and to display differences between more and less effective therapies. Studies of blood and bronchoalveolar lavage samples showed that certain local and systemic immunologic parameters correlate with clinical status and outcome.

A randomized, double-blind trial of single dose piperacillin versus multidose cefoxitin in alimentary tract operations.

For elective alimentary tract operations in which contamination is moderate, single dose prophylaxis with piperacillin is equivalent to triple dose cefoxitin, a well established and effective regimen. Both methods failed to control infection arising in the perineal wound after abdominoperineal resection. Just as is the case with drain site infection, such infection often evolves from postoperative contamination and, indeed, is in theory and in fact unlikely to be controlled by perioperative prophylaxis. This study is among the first of several examining the issue of single dose prophylaxis and will be the harbinger of other studies from other groups examining whether or not the course of therapeutic antibiotics can be safely shortened in patients with peritoneal contamination.

Infection complicating cholecystectomy.

It is important to attempt clinical selection of patients who will benefit from antibiotic prophylaxis during biliary tract operations. Of equal importance is exclusion of patients in whom the risk of adverse effects outweigh the potential benefits. Using clinical criteria defined by Chetlin and Elliott, we have tested a method of defining these patients in our clinical setting. From the size of the sample in this prospective randomized study we can report trends as follows: 1) The incidence of postoperative infection was two times higher in the high-risk group. 2) The incidence of positive bile culture was greater in the high-risk group. 3) Prophylactic antibiotic treatment decreased the incidence of infection in both groups. 4) Radiographic status of the gallbladder is not correlated with subsequent positive bile cultures or incidence of infection. 5) Common duct exploration is associated with a significant increase in incidence of postoperative wound infection. The conclusions of this study substantiate the efficacy of incorporating clinical criteria to determine patients at high risk of developing wound infections.

Effects of muramyl dipeptide and lead acetate on carbon clearance and endotoxin-induced mortality in mice.

Muramyl dipeptide (MDP) is a nonspecific immune adjuvant thought to affect the macrophage. MDP had been used safely without immunosuppressive or toxic side effects in our laboratory and others. Endotoxin, or lipopolysaccharide (LPS), is thought to be responsible for many of the systemic toxic effects of gram-negative infection. Lead acetate potentiates the lethal effects of endotoxin, an effect attributed to increased hepatotoxicity involving both hepatocytes and Kupffer macrophages. This study was undertaken to examine putative mechanism of action of MDP relating to the reticuloendothelial system. Endotoxin was given intraperitoneally to susceptible mice that were pretreated with MDP, lead acetate, or both, and to unmodified controls. Lead acetate significantly enhanced lethality due to LPS, but pretreatment with MDP did not alter mortality. Carbon clearance was measured in mice treated with MDP, lead, or both. There was no difference in the phagocytic index of control mice and those mice treated with lead acetate at various times prior to the injection. Carbon clearance increased significantly in mice pretreated with MDP but was unaltered by the addition of lead acetate. We conclude that if hyperphagocytosis of endotoxin occurs in MDP-pretreated mice, it does not cause additional mortality. Muramyl dipeptide appeared to be a safe reticuloendothelial stimulant that did not enhance the toxicity of lead or LPS in this experimental model.

Second place winner of the Conrad Jobst Award in the gold medal paper competition. Increased antibiotic effectiveness in a model of surgical infection through continuous infusion.

As long as infection remains the most common cause of morbidity and mortality in severely ill patients, there exists the need for more effective anti-infective therapy. The current study was undertaken to determine whether continuous infusion (CONT) is superior to intermittent administration (INT) of an equal amount of cefazolin (CEF) in a model of surgical infection. The thigh suture model consists of the surgical placement of 1 cm of cotton suture with absorbed K. pneumoniae into the thigh muscle of mice. The experimental groups were: 1) controls (n = 20) with thigh suture inoculation and treatment with intraperitoneal (IP) sterile saline; 2) CONT infusion group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by CONT IP infusion at 180 mg/kg/day (n = 22) for 3 days; and 3) INT injection group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by INT IP injections every 8 hours at 180 mg/kg/day (n = 20) for 3 days. All CEF treated animals received identical quantities of total CEF, and all groups were followed for 10 days. The control and INT CEF groups had 20% survival, whereas the CONT CEF group had 81% survival, (P < 0.001). Continuous CEF yielded constant serum levels of 19 +/- 1 micrograms/mL, whereas INT injections resulted in peak serum level of 74 +/- 12 micrograms/mL at one minute but declined to 3.9 +/- 0.9 micrograms/mL in 2 hours. Although there was statistically significant tissue bacterial growth in the INT injection group, there was extensive tissue bacterial clearance in the CONT infusion group.(ABSTRACT TRUNCATED AT 250 WORDS)

A reassessment of the influence of steroids on neutrophil phagocytosis.

The impact of corticosteroids on host defense processes has been studied frequently because of its obvious clinical significance in many surgical patients. A technique that quantifies intraleukocyte iodination was used to measure polymorphonuclear leukocyte phagocytosis in heat inactivated and nonheat inactivated sera in the presence of two different corticosteroids: hydrocortisone sodium phosphate (HSP) and methylprednisolone sodium succinate (MSS). HSP produced a significant reduction in phagocytosis in the cells of healthy subjects when both heat inactivated autologous and isologous serum samples were used. MSS showed no such effect. Conversely, MSS produced a significant reduction in phagocytosis in the cells of healthy subjects when nonheat inactivated autologous serum was used but not when isologous serum was used. These data generally tend to confirm previous studies suggesting that MSS is less deleterious to some host defense processes than HSP and may be the steroid of choice when infection threatens the recipient.

Evaluation of copovithane as a nonspecific immunomodulator in surgically simulated sepsis.

Copovithane (CPV), a synthetic polymer, has been shown to have antitumor activity and also to reduce mortality in experimental murine peritonitis. The purpose of this study was to compare CPV with muramyl dipeptide (MDP), an immunomodulator of proven efficacy in simulated surgical infection. Six groups of CBA/J mice were compared; they received intramuscular injections of normal saline (controls), MDP (100 micrograms), or CPV (100, 200, and 400 mg/kg) 24 h prior to bacterial challenge. The challenge consisted of a Klebsiella-impregnated thigh suture. The first experiment assessed survival after bacterial challenge. The MDP and the CPV groups both had median survival times of 3 days, significantly longer than the control group (1 day, p less than .05). In the second experiment, animals were sacrificed at 6, 24, and 48 h following bacterial challenge, and blood and infected muscle were taken for quantitative bacteriology. At 6 h, there was no difference between groups. Both the MDP and CPV groups had significantly (p less than .05) lower blood bacterial counts than the control group at 24 and 48 h. Both the MDP and CVP groups had significantly lower local bacterial recovery than controls at 48 h (p less than .05), and local bacterial recovery of the MDP group was significantly lower than the control group at 24 h (p less than .05). CPV improved survival and reduced local and systemic bacterial recovery compared with controls. Although the effect of CPV was similar to MDP in this model, it consistently was of lower magnitude and had a narrow dose range.

The histopathology of small arteries following experimental microvascular anastomosis.

We studied the histopathological changes present at various intervals after microsurgical anastomoses in the femoral arteries of 30 rats. The principal findings were (1) widespread loss of intima, (2) widespread necrosis of media, and (3) dehiscence of sutures. The possible causes for these, and their possible significance, are discussed.

In vitro characteristics of tobramycin-PMMA beads: compressive strength and leaching.

Antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement beads have been used as a local drug delivery system for the treatment of bone and soft tissue infections. The beads deliver a high local level of antibiotic with a decreased risk of toxic systemic levels. This study was undertaken to determine the antibiotic release characteristics of tobramycin-impregnated beads over time and to determine the compressive strength of these beads. Acrylic resin (PMMA) bone cement beads were prepared with three different concentrations of tobramycin. The beads were tested for compressive strength, and their antibiotic release characteristics were determined over a 21 day period by radioimmunoassay and by biological testing against a variety of bacteria. The compressive strength of the beads was found to be adequate to avoid fragmentation during their clinical use. There was gradual release of tobramycin from the beads over the entire 21 days, but the release was most marked during the first 48 hours. There was antibiotic activity against both gram-negative and gram-positive organisms, except Enterococcus, for the entire 21 day period. The release of tobramycin followed a curvilinear relationship and was directly related to the initial antibiotic concentration of the bead. Tobramycin-impregnated polymethylmethacrylate beads may represent a reliable method of local antibiotic delivery with sustained activity against a broad spectrum of organisms.

Regional and systemic immune responses in a murine model of empyema.

The extent to which circulating leukocytes reflect functional capacity at the site of infection is unclear despite a century of debate. We conducted experiments designed to clarify those relationships as well as the relationship of pleural and peritoneal responses to infection. Empyema was established in inbred CBA/J mice by introducing Escherichia coli and Bacteroides fragilis into the thoracic cavity through a limited thoracotomy. Walled off abscesses appeared seven days after the introduction of infection. Cell surface expression of murine class II major histocompatibility antigen was measured in peripheral leukocytes, thoracic and peritoneal cavity exudate leukocytes and abscess cells for 60 days after the introduction of infection. The peripheral antibody response was determined by measuring immunoglobulin M (IgM) and immunoglobulin G (IgG) specific for the two organisms. The results demonstrated that, after introduction of infection into the thoracic cavity, mice mounted a specific systemic humoral immune response by producing IgM and IgG. There was a pronounced concomitant cellular response in thoracic and peritoneal cavity exudate cells. However, there was no evidence of a systemic cellular response in circulating lymphocytes or monocytes and polymorphonuclear leukocytes measured as a single group. We conclude from these experiments that measurements of peripheral immune parameters may adequately reveal the humoral response to infection, but it does not reflect the local immune cellular response. Furthermore, a special relationship exists between the peritoneal and the thoracic cavities, whereby an inflammatory process in the thoracic cavity leads to a marked activation of inflammatory process in the peritoneal cavity without affecting peripheral circulating cells to the same extent.

Antibiotic activity in surgical incisions. The basis of prophylaxis in selected operations.

Perioperative antibiotic administration to produce systemic effects reduces the frequency of operative wound infection in selected procedures. Controlled clinical trials now indicate that cephalothin sodium may not be effective in this role, whereas cephaloridine and cefazolin sodium have been beneficial. Review of estimates of incisional antibiotic concentrations taken during prospective patient studies display patterns compatible with these data. EAch drug reaches acceptable incisional concentrations, which are relatively well maintained for cephaloridine and cefazolin; cephalothin disappears from human incisions so rapidly as to provide little wound protection in operations lasting more than one hour.

Bacterial inoculum and the activity of antimicrobial agents.

Experimental and clinical infections have concentrations of bacteria that are greater than the concentrations used in the laboratory for the determination of in vitro activity. When realistic concentrations are used, the antibiotic activity is reduced. The optimum selection of antibiotics may require a re-examination of the laboratory procedures for the determination of sensitivity data.

Effects of pure or combined inocula of Escherichia coli and Bacteroides fragilis on the liver and related metabolism.

To test for synergy between a facultative and anaerobic bacterium and the role hepatic hypoxia may have in its development, rats were subjected to intravascular infusion of 10(8) Escherichia coli, 10(9) Bacteroides fragilis, or a combination of both. Acute effects were evaluated by selected 6-hour measurements, including hepatic pO2, and longer range effects by liver cultures and histology in rats surviving 7 days. During the acute period, systemic arterial pressure and pO2 in bacteremic groups did not differ from saline-infused controls. However, hepatic oxygen supply was significantly reduced in E. coli rats and those given the combined bacteria (mean hepatic pO2 less than 10 mm. Hg versus 20.8 mm. Hg in controls). Significant increases of plasma lactate and pulse rate were also recorded. By comparison, hepatic pO2 was not reduced significantly in the B. fragilis rats, and pulse rate was similar to controls. Plasma lactate, however, increases more rapidly than in other groups. Survival rates were 100 per cent in the B. fragilis group, 88 per cent in the E. coli group, and 65 per cent in the combined group. The difference between the latter groups was not significant. Hepatic histology was normal in rats of the B. fragilis group at 7 days postchallenge. In survivors of the E. coli and combined inoculum groups, there was evidence of anoxic damage and occasional foci of neutrophilic infiltration. Liver cultures were more often positive in rats of the combined inoculum group (p less than 0.05), most often for E. coli, than in the other groups. In summary, although the acute effects of E. coli were not changed appreciably by combination with B. fragilis, the higher rate of E. coli liver infection in survivors suggests that its viability was enhanced. The role of hepatic hypoxia in this remains unclear. It is feasible that hypoxic foci provided temporary protection for B. fragilis, enabling the organisms to affect favorably the survival of E. coli.