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Biomedical subjects

H C Polk

Publications and source records attributed to H C Polk.

At least 163 records · Page 9Linked to original sources

Leaks and obstruction after gastric resection.

Postoperative gastric retention may be minimized by avoiding the use of the Billroth I reconstruction when a large duodenal ulcer must be retained. Postoperative gastric retention is more likely to remit with conservative therapy if the procedure was a Billroth I reconstruction with a vagotomy. In other instances where there is difficulty in gastric emptying, a mechanical cause should be strongly suspected. The optimum duration of a conservative trial with suction for postoperative gastric retention may be debatable, and contrast radiography or endoscopy may be helpful; however, patience and suction are not long-term substitutes for a needed operation.

Adult↗

Effects of muramyl dipeptide and clindamycin in a murine abdominal abscess model.

Peritonitis and subsequent local and remote complications are an important source of morbidity and mortality, which persist despite the best available treatment. Reasonable therapeutic efforts, therefore, have included stimulation of host defenses with immune adjuvants, recently typified by muramyl dipeptide (MDP). Murine abdominal abscesses were created by intraperitoneal injection of Bacteroides fragilis and autoclaved fecal suspensions, and the effects of MDP and clindamycin on these abscesses were evaluated. At 10(4) colony-forming units (CFU) per milliliter of Bacteroides fragilis, intraperitoneal clindamycin was effective in reducing both the incidence of abscess formation as well as the number of abscesses per mouse as compared with controls at doses of 5 mg/kg and 2 mg/kg (P less than 0.01). The effect was more significant when the drug was given 30 min prior than when given after injection of organisms (P less than 0.02). At 10(7) and 10(8) CFU/ml, pretreatment with MDP increased abscess formation (P less than 0.05, P less than 0.01), an effect that was obscured by clindamycin administration, which decreased number of abscesses from controls irrespective of pretreatment with MDP. Abscesses were present on the third day after injection, and MDP, paradoxically, had increased the number of abscesses by the fifth day. Clindamycin reduced abscess formation at all concentrations of bacteria and had a dose and time-dependent response. MDP increased abscess formation only at high concentrations of Bacteroides fragilis, but clindamycin abolished this effect and reduced the number of abscesses to similar levels in both the clindamycin alone and clindamycin + MDP groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Muramyl dipeptide protects decomplemented mice from surgically-induced infection.

Muramyl dipeptide (MDP) is a natural product of bacterial cell-wall breakdown, which can now be produced synthetically; it is the smallest component of the mycobacterial cell wall capable of reproducing the adjuvant activities of Freund's complete adjuvant. We tested the well-documented, protective effect of MDP to increase survival in a murine model simulating surgically-induced bacteremia. The protocol involved the bacterial innoculation of control and decomplemented mice in the presence and the absence of pretreatment with MDP. Bacteremia in both the control and decomplemented groups pretreated with MDP was decreased statistically at 24 h (P less than 0.01) as compared to controls. Likewise, survival was increased significantly at 24 h (P less than 0.05), 48 h (P less than 0.001), and 72 h (P less than 0.001) using the same group comparisons. We conclude, therefore, that MDP maintains its protective effect in the absence of complement, supporting the view that the mechanism of action of MDP is complement independent.

Acetylmuramyl-Alanyl-Isoglutamine↗

Therapy of primary cutaneous melanoma.

The essential tenets of early recognition, biopsy, and appropriate surgical treatment of melanoma are reviewed. The controversies of elective regional lymph node dissection and isolated limb perfusion are discussed, as well as the newer modalities of immunotherapy.

Biopsy↗

Malignant tumors of the liver.

HCC occurs infrequently in Western countries, with recent increases being reported in California and parts of Europe. Southeast Asia, Japan, and South Africa continue to have a high incidence of this tumor with HBV, cirrhosis, and the ingestion of aflatoxins being identified as probable risk factors. Although the majority of patients present with abdominal pain or mass indicative of extensive tumor, asymptomatic, small HCCs are being detected with increasing frequency. Early detection in high-risk individuals is best accomplished by screening with serum AFP determinations and liver ultrasonography. CT and arteriography are valuable preoperatively in defining anatomy and determining resectability. Five-year survival following resection for cure of HCC ranges from 20 to 40 per cent, with improved survival reported for small asymptomatic tumors. Resection of metastatic liver tumors from colorectal primaries results in 48 per cent 2-year and 24 per cent 5-year survivals, with an additional 5 per cent dying of recurrent cancer after 5 years. Although patients with simultaneous and metachronous metastases do equally well after resection, the presence of four or more individual deposits adversely affects survival. Hepatic artery ligation or embolization can produce a significant palliative reduction in total tumor mass in patients with unresectable liver metastases. Regional chemotherapy using implantable hepatic artery drug infusion pumps is promising, with reports of prolonged survival compared with historical controls. Regional hyperthermia, laser vaporization of tumor, and cryosurgical techniques may prove to have useful roles in the selective treatment of liver cancer in the future. Orthotopic liver transplantation has been successful primarily in those in whom the malignancy is found incidentally in the chronically diseased liver.

Adolescent↗

Factors contributing to fatal outcome after treatment of pancreatic abscess.

The authors analyzed 27 patients with pancreatic abscess treated since 1975 at hospitals affiliated with the University of Louisville School of Medicine. Treatment consisted of careful debridement, abscess drainage, and multiple antibiotics in all patients. Overall mortality was 33%; however, only three of 17 patients treated since 1980 have died. Patients who died were more likely to have bacteremia, a residual abscess, multiple organ system failure, and/or polymicrobial growth on culture of the abscess. The proper use of soft suction drains in a dependent position reduced the rate of residual abscess to 19% compared to 67% in patients not treated in this fashion. The results identify factors that are correlates of death in patients with pancreatic abscess and emphasize the importance of prompt diagnosis and proper treatment.

Abscess↗

Infectious morbidity in extremity fractures.

To review infectious morbidity in extremity fractures, 265 patients with 280 open fractures and 573 patients with closed fractures requiring open reduction and internal fixation (ORIF) were reviewed. Among open fractures, 32 (11%) became infected. Significantly fewer infections occurred in open fractures secondary to gunshot wounds (p less than 0.01) and in the upper extremity regardless of cause (p less than 0.05). Preventive preoperative antibiotics did not appear to affect infection rates. Open fracture infections were consistently with hospital-acquired organisms, and these were consistently resistant to the preventive antibiotic employed. Closed fractures had only 18 (3%) infections after ORIF. Preoperative antibiotics did reduce infection rates compared to rates in patients with no preoperative systemic antibiotics (p less than 0.05). Pathogens in ORIF patients showed a greater preponderance of Staphylococci. In conclusion, preventive antibiotics were only effective in the prevention of infection in the ORIF patients. Open fracture patients consistently develop infections with hospital-acquired pathogens, suggesting that contamination after hospitalization rather than at the time of injury is a major factor.

Anti-Bacterial Agents↗

A systematic study of host defense processes in badly injured patients.

A prospective study of factors predisposing to infection in badly injured patients has disclosed: the dominant roles of two specific parameters: monocyte antigen presenting capacity, and opsonic capacity of diluted serum; the potential value of further assessment of: the predictive value of plots of activated T-cells/total T-cells versus monocyte antigen presenting capacity, the apparent protective effect of the ability to sharply increase specific IgM in response to infection, and the apparent protective effect of cytomegalovirus (CMV) infection in the first 28 days after injury against major bacterial infection; the lack of value of analysis of other T- and B-cell subsets in such patients; and the need to clarify CMV and transfusion status with respect to interpretation of such data. The specific role of variable transfusion and of specific serum immunoglobulins will require further and more discriminating study.

Adolescent↗

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.

Acetylmuramyl-Alanyl-Isoglutamine↗

Establishment of a clinical teaching associates breast examination program for medical students.

A program was designed to instruct medical students on how to obtain a history pertinent to breast abnormalities and to perform a breast examination. The use of clinical teaching associates provides direct student instruction and critiques during the examination. In addition, students are taught how to instruct patients in the breast self-examination and to properly document breast abnormalities. Such a program should be considered for incorporation in all physical diagnosis courses as well as in residency training programs and seminars for practicing physicians.

Breast↗

The enhancement of host defenses against infection--search for the Holy Grail?

With the discovery of new and pharmacologically better described agents, the pursuit of a method for the enhancement of nonspecific host defense against bacterial infection has received a new infusion of interest. Work with the synthetic glycopeptide muramyl dipeptide has indicated its usefulness in a variety of surgically simulated illnesses in experimental animals. The extent of that work is described in detail and current mechanisms of action are explored that focus on the release of transmitter substances from the macrophage, the immediate impact on acute inflammatory cells, and an organ-by-organ dissection of the animal suggesting enhanced containment of experimental infection in animals treated with muramyl dipeptide.

Acetylmuramyl-Alanyl-Isoglutamine↗

Association of chronic cystic mastopathy, xeromammographic patterns, and cancer.

The Breast Cancer Demonstration and Detection Project in Louisville (BCDDP-L) screened 10,128 women for cancer. From this screening, another project evolved wherein those patients diagnosed as having chronic cystic mastopathy (CCM) were followed over a 10-year period to evaluate any association between CCM and breast cancer. In all, 1396 breast biopsies were performed, with 165 cancers being diagnosed either on initial screening or during subsequent years. Three of these are excluded, since histopathologic slides could not be obtained for central review. Of this group, cancer was associated with CCM in 116 specimens and without CCM in 46 specimens. One subset of 355 patients with biopsy-proven CCM but no breast cancer was followed for 6 to 12 years, for a total of 2443.5 woman-years of observation. Within this subset, a total of only four cancers occurred (4 cancers/2443.5 woman-years for 0.00164 cancers/woman-years). This incidence is not significantly different from the expected value. However, an estimate is provided as to the power of the test that could be obtained from a larger sample size derived from other BCDDPs. This group of 355 women was sorted into subsets by establishing a matrix matching ten histopathologic subdivisions of CCM against six subdivisions of Wolfe's xeromammographic (XM) patterns. The numbers of cancers in each cell of this matrix is reported. The results found no concentration of these four cancers in this matrix.

Adult↗

Serum level monitoring of aminoglycoside antibiotics. Limitations in intensive care unit-related bacterial pneumonia.

Serum aminoglycoside assays have been accepted as useful methods of enhancing therapeutic efficacy in the treatment of intensive care unit-acquired pneumonia and in avoiding aminoglycoside nephrotoxicity. We prospectively studied 68 surgical patients with normal renal function and gram-negative bacterial pneumonia who were treated with aminoglycosides. Serum levels indicated subtherapeutic levels in 47 patients and verified optimum levels in 13 patients. Toxic trough levels developed in six patients and, despite immediate dosage adjustment, five patients suffered nephrotoxicity. Six additional patients also had nephrotoxicity. Five of these patients never had toxic peak or trough levels and rising trough levels developed in one patient after serum creatinine levels began to rise. We conclude that routine monitoring of serum levels effectively detects subtherapeutic antibiotic levels. This modality is useful for optimizing dosage schedules, but does not serve to predict or avoid nephrotoxicity in critically ill surgical patients.

Adolescent↗

Leaching of tobramycin from PMMA bone cement beads.

The in vitro leaching characteristics of tobramycin from acrylic resin (PMMA) bone cement beads have been determined by a radioimmune assay. Tobramycin was incorporated at two concentrations into bone cement beads fabricated from three commercial brands of acrylic resin. Antibiotic leaching followed a curvilinear relationship of the form X . Y = A . X + B . Y. All beads showed similar tobramycin leaching rates over time but the initial amount of leached material differed with the amount of tobramycin incorporated in the bead and the source of the PMMA bone cement. The data indicate that tobramycin-impregnated PMMA beads permit antibiotic leaching at a controlled rate compatible with possible clinical application.

Bone Cements↗

Characterization of neutrophil iodination for the assessment of phagocytic and opsonic function in septic patients.

To increase our understanding of the nature of surgical infection, further studies on the host defense abilities of infected patients are required. Therefore, a more thorough investigation of the iodination method for the measurement of polymorphonuclear leukocyte function and serum opsonic activity was undertaken to characterize its application in surgical infection. A significant relationship was found between the phagocytic indices derived from different standard neutrophils or sera measured on the same day. When expressed as a value of normal phagocytic indices minus abnormal phagocytic indices, this relationship was constant from day to day despite wide variations in the absolute phagocytic index values. This finding enables direct comparisons to be made between the values obtained both from the same patient and from different patients during the course of their illness by reference to daily control values. We also found that the system was sufficiently sensitive to detect, in a dose-responsive manner, the changes induced in normal neutrophil phagocytosis and serum opsonic activity by a specific bacterial challenge with either K. pneumoniae or E. coli. In addition, zymosan, which is utilized in the iodination reaction but also has immunoadjuvant properties, was found to enhance neutrophil function but depress serum opsonic activity in the face of such bacterial challenges. We conclude that the iodination technique is a credible method for the indirect measurement of polymorphonuclear phagocytosis and serum opsonic function in the face of a bacterial challenge and can be reliably employed in studies of septic patients provided these findings are taken into account.

Blood Bactericidal Activity↗

Muramyl dipeptide and polymorphonuclear leukocyte chemotaxis in vitro.

Muramyl dipeptide (MDP) is an immunostimulatory agent that has been shown repeatedly to provide protection against the effects of some forms of experimental surgical infection. The mechanisms of this protection are incompletely understood, and in order to further define them, the impact of MDP upon in vitro polymorphonuclear (PMN) leukocyte chemotaxis was examined in the presence of both normal and opsonic depleted serum. We have also evaluated the effect of MDP as a chemoattractant itself and the response of neutrophils along with MDP to a standard chemoattractant, n-formyl-L-methionyl-L-leucyl-L-phenyl-alanine (FMLP), using the agarose assay for chemotaxis. MDP has weak but significant chemotactic activity itself, with a peak effect at a concentration of 5 X 10(-8) micrograms/ml for neutrophils. These effects are enhanced by the addition of 10% serum. MDP more strongly enhances neutrophil chemotaxis to FMLP. The enhancement of chemotaxis may be a factor in the protection that MDP exerts against some experimental bacterial challenges.

Acetylmuramyl-Alanyl-Isoglutamine↗

Unifying concepts in treatment of esophageal leaks.

We treated 75 patients with esophageal trauma, perforation, or anastomotic leak. Several factors were shown to be associated with an increased mortality, including delayed treatment, presence of severe underlying esophageal disease, total parenteral nutrition catheter infection, the necessity for major extirpative procedures to treat the perforation, and the use of exclusion and diversion in the continuity procedure. The use of local muscle flaps to buttress suture line closure has led to excellent results in the 19 patients so treated. Delayed treatment of perforation or an anastomotic leak is a major problem, but the treatment protocol described herein has led to the survival of 12 of 16 patients treated. The use of primary muscle flap closure for extensive esophageal defects or delayed treatment of nonhealing leaks was evaluated in five patients. All five had healing of the defect, with one resultant esophageal stricture.

Dilatation↗