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Biomedical subjects

H C Polk

Publications and source records attributed to H C Polk.

At least 127 records · Page 7Linked to original sources

Re-emphasis of priorities in surgical antibiotic prophylaxis.

The results of two prospective, randomized trials, comparing single dose piperacillin with multidose cefoxitin prophylaxis in elective surgical procedures of the gastrointestinal tract were combined to examine some basic aspects of clinically, applied antibiotic prophylaxis. As there was no difference in the efficacy of prophylaxis between the groups, data from both centers and both drug groups were combined for analysis. Patients whose ages were greater than 40 years, the presence of cancer and the administration of an antibiotic for longer than 60 minutes preoperatively were associated with a higher rate of infectious complications. Duration of operation was also related to subsequent infection, ranging from 6 per cent in procedures lasting less than two hours to 27 per cent in operations lasting more than four hours. There was a greater failure of prophylaxis in patients undergoing rectal procedures, with a 29 per cent rate of infectious complications compared with 14 per cent in patients undergoing operations upon the colon. This difference was present even when duration of operation was taken into account.

Adult↗

Reversal of Adriamycin-impaired wound healing by transforming growth factor-beta.

Impaired wound healing remains an important clinical problem. Treatment with systemic Adriamycin (doxorubicin) is known to impair wound healing in patients, and it has been used to produce animal models of impaired healing. The results of previous studies have shown that local treatment of incisions in normal rats with transforming growth factor beta (TGF-beta) or epidermal growth factor (EGF) stimulated early increases in tensile strength of surgical incisions in normal rats. We investigated the effects of locally applied, biosynthetic TGF-beta or EGF on the tensile strength of standardized incisions in rats treated with Adriamycin. Systemic Adriamycin treatment (8 milligrams per kilogram) produced significant decreases in wound tear strength (WTS) and wound tear energy (WTE) when compared with that of normal rats at seven and ten days (p less than 0.01). A single dose of TGF-beta (2 micrograms) in a collagen vehicle stimulated a reversal of this wound healing impairment at ten days (p less than 0.05), returning the WTS and WTE to near normal levels. A single dose of EGF (50 micrograms) in hyaluronic acid failed to increase tensile strength, probably because of formulation of EGF in a vehicle that does not prolong its release in incisions. These results suggest that exogenous growth factors may be clinically useful in stimulating healing in incisions in healing impaired conditions.

Animals↗

The comparative clearance rates of the pleural and peritoneal cavities.

We compared the rates of bacterial clearance from the pleural and peritoneal cavities of rats after contamination with 1 x 10(6) live Escherichia coli. Pleural clearance was enhanced beginning at 30 minutes after injection and extended to at least six hours. At 24 hours, the clearance was similar for both the pleural and peritoneal groups. Blood and organ bacterial cultures were similar between these two groups. White blood cell populations were similar at rest, but there was a greater increase in the leukocyte population in the pleural cavity six hours after E coli stimulation. We postulate that the increased clearance of E coli from the pleural cavity may be due to differences in lymphatic absorption, recruitment of leukocytes, or fibrin trapping of bacteria.

Animals↗

Depressed interferon gamma production and monocyte HLA-DR expression after severe injury.

Monocyte HLA-DR antigen expression and mitogen-stimulated interferon gamma production were measured sequentially on days 1, 3, 7, 14, and 21 after admission in 20 multiply injured patients (mean Injury Severity Score, 33). Ten patients recovered uneventfully and ten developed a major infection, three of whom died. Trauma resulted in immediate and profound depression of both interferon gamma production and monocyte HLA-DR antigen expression compared with controls. Interferon gamma remained below control levels for all days on which it was measured in all patients. In uninfected patients, interferon gamma production began to recover after day 7 and interferon gamma levels on day 21 were greater than on all other days. Monocyte HLA-DR antigen expression returned to normal between days 7 and 14 in uninfected patients, despite subnormal production of interferon gamma. Failure to increase interferon gamma production and monocyte HLA-DR antigen expression was associated with an episode of major infection. We postulate that stimulation of the immune system early after injury may reverse the defects reported and decrease the incidence of infection after severe trauma.

Adolescent↗

The natural history of murine intra-abdominal abscess formation.

We determined the natural history of experimental abscess formation and had a secondary interest in the effect of muramyl dipeptide. Swiss-Webster mice were injected intraperitoneally with autoclaved mouse fecal suspension and either Bacteroides fragilis (10(8) colony-forming units [cfu]/mL) alone or Escherichia coli (10(4) cfu/mL), enterococcus (10(3) cfu/mL), and B fragilis (10(5) cfu/mL) after pretreatment with muramyl dipeptide or saline solution. All deaths occurred within 48 hours of injection and surviving mice, including those bearing abscesses, appeared to be healthy throughout the study. The number of mice with abscesses and the number of abscesses per group were at their maximum at two to four weeks. Groups with live bacteria had a substantial reduction in the number of abscesses between eight and 26 weeks, compared with two- and four-week values. Manual rupture of palpably large eight-week-old abscesses in 21 mice produced only one death and at autopsy two weeks later, all of the mice showed multiple smaller abscesses. Abscess formation appeared to be beneficial and the natural history of such may include spontaneous resolution without mortality.

Abdomen↗

A systemic study of enhancement of host defense processes against bacterial infection.

A sequence of studies over more than two decades has identified a variety of host defense abnormalities that may contribute to clinical infection in high risk and/or badly injured patients. Clearly, animal studies set the stage for our clinical applications and suggest that a variety of so-called non-specific host defense stimulants may indeed correct many of these abnormalities and promote the ultimate control of surgical infections.

Adjuvants, Immunologic↗

Multiple adenocarcinomas of the colon and rectum. An analysis of incidences and current trends.

Three hundred forty-five colorectal cancers were identified in 320 patients over a nine-year period. Twenty-one patients (7 percent) had synchronous cancers. Metachronous cancers were identified in five patients (2 percent). Thirteen of the synchronous cancers were foci of invasive adenocarcinoma in polyps with elements of benign neoplastic tissue. There was a trend for younger patients to have multiple colon cancers. Fifteen percent of the synchronous colon cancer patients were less than 50 years of age. The mean age of patients who presented with metachronous cancer was 54, and 11 years was the average time interval between the diagnosis of the initial and the metachronous tumor. Colonoscopy proved to be more reliable than barium-enema examinations in identifying synchronous cancers. It is concluded from this review that before elective resections, colonoscopy should be used to effectively screen patients for synchronous cancers, and following curative resection, the residual colon should be periodically examined for the remainder of the patient's life.

Adenocarcinoma↗

An outcome predictive score for sepsis and death following injury.

Injury is an important cause of both morbidity and mortality, particularly in the young. Scoring systems have been developed to establish guidelines of transfer and compare patient outcome, but no scoring system as yet has been constructed that focuses upon immune capability of these patients. We report an outcome predictive score (OPS) which appears to distinguish good outcome from sepsis in patients who survive, and between patients with sepsis who survive from patients with sepsis who die. The score is based on (1) Injury severity score (ISS) expressed as percentage of the 50 per cent lethal dose of injury for age (%LD50), (2) Degree of bacterial contamination at initial injury, (3) The patient's monocyte DR antigen expression. Fifty-one severely injured patients were divided into three groups: (1) A group without infection (N = 15), (2) A major sepsis group which survived (N = 24), (3) A group who died (N = 12). There was no difference between the ISS of these groups. The mean OPS of the good outcome group was significantly less than the mean OPS of both the septic (P less than 0.0002) and dead (P less than 0.00001) groups. The mean OPS of the septic group was also significantly less than the mean of the group that died (P less than 0.002). Identification of high risk patients may be important to determine priority of patient care and to institute additional therapeutic measures.

HLA-DR Antigens↗

Effects of interferon-gamma treatment on surgically simulated wound infection in mice.

Interferon-gamma (IFN-gamma) has been shown to have immunoregulatory properties and is able to modulate resistance to several microbial infections. This study was designed to determine the efficacy of IFN-gamma treatment in a mouse model of infection that simulates many clinical conditions associated with surgical wound infection: viz, a bacteria laden suture and tissue injury. The test bacteria were Klebsiella pneumoniae. Groups of CBA/J mice received either IFN-gamma or RPMI-1640 medium (controls) subcutaneously. IFN-gamma was administered daily at a dose of 7500 units for 5 days prior to bacterial challenge. Mice treated with IFN-gamma survived significantly longer than controls. Systemic bacterial recovery was significantly reduced in the IFN-gamma treated group but local bacterial recovery was unaffected.

Adjuvants, Immunologic↗

Successful treatment of empyema thoracis with polymethylmethacrylate antibiotic-impregnated beads in the guinea pig.

Two hundred nine Duncan-Harley guinea pigs had intrathoracic inoculation with 10(8) Staphylococcus aureus, accompanied by blood and umbilical tape. One hundred fifty-two animals were excluded because of clinical recovery, early death, or complications related to intrathoracic polymethylmethacrylate (PMMA) bead placement. The remaining 57 animals had clinical signs of empyema thoracis and were the subjects of this study. Group I animals (N = 24) served as the controls and had no therapy. Group II animals (N = 14) were treated by intrathoracic placement of placebo PMMA beads. Group III animals (N = 19) were treated by intrathoracic placement of tobramycin sulfate-impregnated PMMA beads. There were no differences between the groups in pleural reaction or pneumonia scores. These findings demonstrate a similar host response to the established infection. Group III, however, had a higher sterilization rate than Groups I and II (p less than 0.05), a finding underlining the therapeutic effect of tobramycin-treated PMMA beads. We conclude that intrathoracic local antimicrobial therapy with slow-release tobramycin-impregnated PMMA beads may enhance empyema treatment by increasing the rate of local sterilization. More experiments are necessary to assess the efficacy of this potentially important therapeutic arm for the treatment of thoracic empyema.

Animals↗

Effect of interferon-gamma treatment on the course of a burn wound infection.

Interferon-gamma (IFN-gamma) has been shown to have immunoregulatory properties and is able to modulate resistance to several microbial infections. This study was designed to determine the efficacy of IFN-gamma treatment in a murine burn wound infection model. Bacterial challenge consisted of Klebsiella pneumoniae (10(8) organisms/ml) or Pseudomonas aeruginosa (10(8) organisms/ml), applied topically immediately after burning. Groups of CBA/J mice received either IFN-gamma or RPMI-1640 medium (controls) subcutaneously. IFN-gamma was administered daily at a dose of 7,500 units for 5 days prior to bacterial challenge. Burn without bacterial challenge produced no mortality. Mice treated with IFN-gamma survived significantly longer than controls when the bacterial challenge was K. pneumoniae. There was no difference in survival when bacterial challenge was P. aeruginosa. The Ia antigen expression of peripheral blood mononuclear cells was severely reduced for 3 days post-burn. This drop was prevented on day 3 post-burn in mice treated with IFN-gamma. These data indicate that interferon was effective treatment in a murine model of Klebsiella burn wound infection and was associated with maintenance of Ia antigen expression that may have contributed to the action of the IFN-gamma.

Animals↗

The capacity of serum to support neutrophil phagocytosis is a vital host defense mechanism in severely injured patients.

The opsonic capacity of patient serum was studied in 43 trauma patients of whom 13 recovered uneventfully, 21 developed major infection, and nine died, mostly of infection. Blood samples were taken within 24 hours of injury. Fifteen patients were studied serially of whom 14 developed severe infection and/or died. Opsonic capacity was determined by flow cytometry and measured as the ability of normal neutrophils to phagocytose killed bacteria previously incubated with patient serum. The most dilute sera reflected changes for better and worse most clearly. On initial assessment, those who died of sepsis showed a 61% mean fluorescent intensity (MFI), which was significantly lower than the 99% MFI for those who survived infection (p less than 0.01) and the 78% MFI of those who developed no infection (p less than 0.05). Serial samples demonstrated a super serum response in four of seven patients surviving major sepsis but in none of the seven who died of infection.

Adult↗

More is better. Antibiotic management after hemorrhagic shock.

Previous reports suggest that standard antibiotic prophylaxis is ineffective in reducing the incidence of wound infection after hemorrhagic shock. This study investigated the use of larger and longer doses of antibiotic in a model of staphylococcal infection after hemorrhagic shock. Sprague-Dawley rats resuscitated from hemorrhagic shock were injected with either 10(6), 10(8) or 10(10) Staphylococcus aureus subcutaneously. Five treatments were investigated: 1) control (no antibiotic), 2) short-course cefazolin (CEF) (SHORT), 30 mg/kg intraperitoneal (IP), 30 minutes before and 4 hours after inoculation, 3) long-course CEF (LONG), 30 mg/kg IP, 30 minutes before and 4 hours after inoculation, and thereafter, every 8 hours for 3 days, 4) mega-CEF (MEGA) 200 mg/kg IP, 30 minutes before and 4 hours after inoculation, and 5) mega-long CEF (MEGA-LONG), 200 mg/kg IP, 30 minutes before and 4 hours after inoculation, and thereafter, every 8 hours for 3 days. Abscess number, weight, and diameter were measured on Day 7. At the 10(6) inoculum, SHORT was effective in both shocked and unshocked animals. In the 10(10) group, all antibiotic regimens decreased the 100% mortality that followed shock without treatment, but they had little effect on abscess formation. In unshocked rats at the 10(8) inoculum, SHORT was effective in reducing abscess number, diameter, and weight (all p less than 0.05 vs. control). After hemorrhagic shock, SHORT did not decrease abscess frequency, but it did diminish abscess diameter. LONG significantly decreased abscess diameter and abscess weight (both p less than 0.05). After shock, both MEGA and MEGA-LONG reduced abscess number (p less than 0.05 vs. control) and MEGA-LONG was superior to all other regimens at the 10(8) inoculum. These experimental data show that increasing both the dose and duration of antibiotic administration is more effective than standard short-course antibiotic prophylaxis in preventing experimental infection after hemorrhagic shock.

Abscess↗

Modulation of infection by gamma interferon treatment following trauma.

Gamma interferon (IFN-gamma) has been shown to be able to modulate several microbiol infections, perhaps as a result of the immunoregulatory properties of this interferon. The present study was designed to determine the efficacy of IFN-gamma treatment in a mouse model of infection that simulates clinical conditions occurring following abdominal trauma. In this model, mice were first infected intraperitoneally with Escherichia coli and then underwent immediate surgical laparotomy. Finally the mice were secondarily infected intramuscularly with Klebsiella pneumoniae. Groups of CBA/J mice received either IFN-gamma or RPMI 1640 medium (controls) subcutaneously. IFN-gamma was administered daily at a dose of 7,500 U, commencing 1 h postlaparotomy and continuing until the second bacterial challenge. Mice treated with IFN-gamma survived significantly longer than controls. The Ia antigen expression of peripheral blood monocytes was severely reduced in animals for 3 days after laparotomy and for 5 days after laparotomy and infection. This drop in Ia antigen expression was prevented in animals treated with IFN-gamma. These data indicate that IFN-gamma had a beneficial effect in a model simulating bacterial infection after trauma and that maintenance of Ia antigen expression in interferon-treated mice may have contributed to the observed therapeutic effect.

Adjuvants, Immunologic↗

Value of diagnostic laparoscopy in young women with possible appendicitis.

Removal of a normal appendix because of suspected appendicitis occurs most frequently in women of reproductive age. We investigated the value of laparoscopy in the diagnostic evaluation for possible appendicitis in women of childbearing age. Fifty-one women were entered in a management protocol, which included diagnostic laparoscopy in instances with atypical features. Twenty patients underwent immediate appendectomy because of history and physical findings classical for appendicitis; 31 women with atypical history and physical findings underwent an initial diagnostic laparoscopy. In the group of patients who underwent immediate appendectomy because of classical presentation, five of the appendices removed were normal. At laparoscopy, appendicitis was diagnosed in five patients, another disease in 15 and no diagnostic abnormality was found in six. Five patients had a normal appendix removed, two because of questionable inflammation and three because of nonvisualization of the appendix. There were no false-negative examination results. Twenty-one patients required no further operative intervention after laparoscopy. The negative appendectomy rate remained unchanged (ten negative appendectomies of 30 performed). Definitive diagnoses of eight instances of pelvic inflammatory disease, six of ruptured ovarian cysts and one instance of ileitis of the small intestine were made earlier than would have been possible without diagnostic laparoscopy in this setting. Diagnostic laparoscopy permits earlier definitive diagnosis and prompt institution of appropriate therapy for disease of the female reproductive tract that simulates appendicitis. Caution is advised, however, when diagnostic laparoscopy is applied more frequently than right lower quadrant exploration in the management of probable appendicitis. The improvement in diagnostic accuracy may be offset by an increased number of negative appendectomies resulting from nonvisualization and false-positive inflammation.

Adult↗

Modulation of Klebsiella pneumoniae infection of mice by interferon-gamma.

The aim of this study was to determine the efficacy of interferon-gamma (IFN-gamma) as prophylaxis and therapy in a wound infection model with a 'surgical' pathogen. The bacterial challenge consisted of intramuscular injections of Klebsiella pneumoniae (10(3) organisms in 0.1 ml). Groups of 12 CBA/J mice had either IFN-gamma or RPMI-1640 medium (controls) injected subcutaneously. Mice pretreated with IFN-gamma in a dose of 7,500 or 750 units per day, followed by infection and 2 days additional IFN-gamma treatment, survived significantly longer than controls or mice treated with 150 units of IFN-gamma per day. Significantly greater survival than controls was seen with only 5 or 3 days pretreatment with IFN-gamma but not with 1 day pretreatment. Administration of IFN-gamma to the opposite hind leg from the one receiving bacterial challenge was as effective as same leg treatment. When IFN-gamma therapy was commenced 1 h after bacterial challenge and continued for 7 days, 13 of 60 mice survived, which was significantly greater than four of 60 surviving controls. These effects may be secondary to IFN-gamma's immunoregulatory effects rather than by involving any antiviral properties.

Animals↗

Open treatment of peritonitis: an argument against.

We conclude that open management of advanced peritonitis may provide improved drainage, but it does so at an intolerable cost of increased mechanical lesions, namely, fistulas. The theories of animal investigators need to be tested at the bedside and in the hospital operating room before this idea receives any further consideration. "Semi-open" treatment has been widely and usefully used by many surgeons. Unfortunately, it provides less than total drainage and has its own set of major problems related to mesh removal and/or ultimate wound closure. We think that a better alternative for future controlled study is the sporadically espoused but impressively effective continuing peritoneal lavage with dilute solutions of antibiotics.

Anti-Bacterial Agents↗

Evaluation of endoscopy training in a general surgery residency.

To evaluate the gastrointestinal endoscopy training program, a survey of the 33 former chief residents, who finished our program in 1981-1986, was conducted. All 33 graduates responded; 22 graduates are general surgeons, 11 completed or are completing training in a surgical specialty. Eighteen of the 22 general surgeons routinely perform endoscopy in their practice. Graduates in cities with a population greater than 250,000 are as likely to perform endoscopy as the surgeons who live in smaller communities. Ninety one per cent consider endoscopy training to have been an important part of their surgical training. Based on this assessment, endoscopy training is an important part of a general-surgery residency.

Colonoscopy↗