PubMed Health⌕ Search

Biomedical subjects

W G Cheadle

Publications and source records attributed to W G Cheadle.

At least 91 records · Page 5Linked to original sources

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↗

Combined cimetidine-alginate antacid therapy versus single agent treatment for reflux oesophagitis: results of prospective double-blind randomised clinical trial.

This randomised double-blind study compared the effects of cimetidine 400 mg four times daily (q.d.s.), Gastrocote (alginic acid, aluminium hydroxide gel, magnesium trisilicate, sodium bicarbonate) two tablets q.d.s. and a combination of both on ambulatory 24-hour oesophageal pH, endoscopic findings and symptoms in patients with reflux oesophagitis. Patients were treated for ten weeks with assessments at entry, after four weeks and at the end of the study. Before treatment, oesophageal pH was less than 5.0 for 25% overall of the 24 hours monitoring in all three treatment groups. After ten weeks, the percentage of time with an oesophageal pH less than 5.0 was 26% on Gastrocote, 26% on cimetidine and 14% on the combination (P less than 0.05, combined therapy versus cimetidine alone). The severity of the heartburn was reduced on all three treatments. The average number of days with heartburn per week was 5.0, 3.6 and 3.4 in the Gastrocote, cimetidine and combined groups respectively. The difference between Gastrocote and the combination was statistically significant (P less than 0.05). There was a clear trend towards improvement of endoscopic oesophagitis at ten weeks in the combined therapy group when compared to single agent treatment with cimetidine or Gastrocote although the difference was not significant due to inadequate numbers. This study indicates that combined cimetidine and Gastrocote is a more effective treatment for reflux oesophagitis than single agent therapy with either drug.

Alginates↗

The response of immunoglobulins to infection after thermal and nonthermal injury.

Traumatic and thermal injuries are leading causes of mortality and morbidity due to their high incidence of infection. Host defense is vital to recovery in these patients yet incompletely understood. On days 1, 7, and 14, serum immunoglobulins of the IgA, IgG, and IgM classes were measured in 46 consecutive patients who sustained severe trauma with an injury severity score of at least 20. The patients were divided into four groups: 1) an uneventful recovery group (n = 11) of nonthermal trauma patients who did not become infected; 2) an infected nonthermal group without splenectomy; 3) an infected group of burn patients; and 4) 12 patients who underwent splenectomy of which nine became infected following nonthermal trauma. In each patient group, IgA, IgG, and IgM were all reduced, and group 1 had a steady return to normal range. Group 2 patients exhibited supranormal responses in all 3 classes at one week and supranormal IgA and IgG responses at two weeks. In contrast, both infected burn and splenectomized patients had markedly reduced IgG and IgM levels compared with the group 2 patients (P less than 0.05). Splenectomy sharply reduced IgM response to infection at 7 and 14 days compared with nonsplenectomized infected posttraumatic patients. Immunoglobulin response after trauma depended on the type of injury, presence of infection, splenic function, and type of immunoglobulin. Recognition of immunoglobulin deficiencies in both the burn and splenectomized patient may permit focused therapy, such as specific replacement of these proteins.

Burns↗

The importance of early diagnosis of small bowel obstruction.

The records of 300 patients with a diagnosis of small bowel obstruction were evaluated to determine which factors, if any, were prognostic of clinical outcome. Ninety per cent of patients had at least one prior abdominal procedure; those of a gynecologic or obstetric nature were most common. Abdominal pain (92%), vomiting (82%), abdominal tenderness (64%), and distention (59%) were the most frequent symptoms and signs, and plain abdominal x-rays were abnormal in 273 (91%) patients. Two hundred and nine patients (70%) underwent surgical repair, of which 48 (23%) required resection of intestine for densely adherent or strangulated bowel. Contrast studies were generally not helpful and associated with barium peritonitis in two patients. The mortality rate for the entire series was 9 per cent, which doubled for those who underwent resection. Septic complications occurred in 31 per cent of the survivors in this group. Fourteen of the 16 patients who died from abdominal sepsis had a delay in presentation and/or treatment, which was the most important prognosis factor for patient outcome.

Female↗

The effect of alcohol on nocturnal gastroesophageal reflux.

The effect of 120 mL (4 oz) of scotch whiskey (40% alcohol) on nocturnal gastroesophageal reflux was studied by ambulatory esophageal pH monitoring. Seventeen healthy volunteers were studied on two occasions, using a computerized radiotelemetric esophageal pH monitoring system. The subjects were given the alcohol during the second session, three hours after the evening meal, and went to bed at their usual time. Seven of the 17 subjects had prolonged supine reflux episodes on the night of alcohol ingestion. These lasted an average of 47.1 minutes (23.2 to 91.8 minutes) and occurred on an average of 3 1/2 hours after ingestion of whiskey and 1.4 hours after lying down. None of the subjects had these episodes on the control night. There was also a significant acidic shift in the cumulative percentage of data points below a pH of 3 and a pH of 4 in the supine position on the night of alcohol ingestion compared with the control night. This study has shown that there was a significant exposure of the distal esophagus to acid and that the normal acid clearance of the esophagus in the supine position was impaired after only moderate amounts of alcohol.

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↗

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↗

Prophylactic postoperative nasogastric decompression. A prospective study of its requirement and the influence of cimetidine in 200 patients.

To determine the need for prophylactic nasogastric decompression following laparotomy and the influence of cimetidine, 200 consecutive patients who underwent major abdominal procedures were prospectively randomized into one of four limbs: no tube-placebo; no tube-cimetidine; tube-placebo; and tube-cimetidine. Patients were evenly distributed among these groups with respect to age, sex, alcohol and tobacco use, previous operations, and types of operations. There was significantly longer time until passage of flatus, bowel movement, and cessation of intravenous fluids in the tube group (p less than 0.05). Duration of postoperative stay increased from 11.4 to 14.1 days in the intubated patients (p less than 0.05). There was also significantly more pain with and frequency of swallowing, and nose/throat discomfort in the tube group. Nasogastric tubes reduced the incidence of vomiting from 28 in the no-tube group to 10 in the tube group (p less than 0.05), but most had only one or two episodes. Cimetidine did not affect either the incidence of vomiting or the duration of intubation, but was associated with a significant increase in pneumonias (p less than 0.05). Five patients without tubes initially, and seven patients with tubes had to have them inserted or replaced for vomiting or abdominal distention, which occurred equally in the placebo and cimetidine limbs. There were no cases of aspiration pneumonia, gastric dilatation, or wound dehiscence in the trial, and the four anastomotic leaks were divided equally between the tube and no-tube groups. The results indicated that prophylactic decompression was unnecessary in most patients and associated with increased morbidity and delayed return of gastrointestinal function. Cimetidine lowered nasogastric output on the first postoperative day (p less than 0.05), but did not prevent vomiting.

Cimetidine↗

Pyloric reconstruction for severe vasomotor dumping after vagotomy and pyloroplasty.

The performance of vagotomy and pyloroplasty is followed by the occurrence of dumping symptoms in 10-30% of patients. In a few, these are severe, persistent, and refractory to dietary and medical management. Pyloric reconstruction was performed in nine patients with severe dumping symptoms. All patients were treated conservatively for at least 1 year before reconstruction. Gastric emptying studies, using a 99mTc-sulphur colloid labeled 15% dextrose, were performed before and after reconstruction in each case. All were Visik grade IV before surgery. After pyloric reconstruction, interviews were conducted by a separate clinician not involved in any management of the patients. Overall improvement was obtained in eight of nine patients. Four patients improved to Visik grade II, and four to Visik grade III. With regard to dumping symptoms only, seven of nine were improved to Visik grade II. All patients had double exponential gastric emptying curves before surgery, and six of the nine reverted to single exponential curves similar to those of unoperated controls. The initial 10-minute emptying rate was significantly decreased (p less than 0.05), and the per cent retention at 60 minutes (p less than 0.02) was significantly increased. Improvement in gastric emptying correlated well with relief of symptoms. Pyloric reconstruction is relatively simple and corrects rapid gastric emptying at the gastric outlet. These results indicate that pyloric reconstruction significantly benefits most patients with severe dumping symptoms and should be considered as the initial remedial procedure for dumping after pyloroplasty.

Dumping Syndrome↗

Muramyl dipeptide increases tolerance to shock and bacterial challenge in mice.

We measured the phagocytic capacity of the reticulo-endothelial system by assay of the clearance of colloidal carbon from the blood stream in both normal mice and mice in which shock had been induced by intraperitoneal injection of hypertonic glucose. The group of shocked mice was further subdivided into those pretreated with the immunoadjuvant, muramyl dipeptide (MDP), and those given placebo. Shock reduced reticulo-endothelial phagocytosis (P less than 0.01), whereas pretreatment of shocked mice with MDP led to a hyperphagocytic state (P less than 0.01). In a second series of experiments we subjected shocked mice, pretreated with MDP or placebo, to a virulent Klebsiella pneumoniae infection. MDP significantly improved survival (P less than 0.01).

Acetylmuramyl-Alanyl-Isoglutamine↗

Combined topical and systemic antibiotic prophylaxis in experimental wound infection.

The effectiveness of a combined topical and systemic antibiotic regimen was studied in an animal model previously shown to simulate clinical surgical wound infection. At a high level of bacterial contamination, the combination regimen produced a lower infection rate than either a placebo (p less than 0.01), a topical antibiotic administered alone (p less than 0.01), or a systemic antibiotic administered alone. At a lower level of bacterial contamination, no additional reduction in infection rates was produced by the combination regimen when compared with systemic antibiotic administered alone. These experimental results suggest that when wound contamination is great, a combination of topical and systemic antibiotics is the more effective regimen. Where wound contamination is less severe, systemic antibiotic prophylaxis is all that is required; no further benefit is obtained by the additional administration of topical antibiotics. Clinical trials appear justified to confirm or refute this hypothesis.

Administration, Topical↗

Computerized 24-hour ambulatory esophageal pH monitoring and esophagogastroduodenoscopy in the reflux patient. A comparative study.

Ambulatory 24-hour esophageal pH monitoring and esophagogastroduodenoscopy were performed in 72 patients with symptoms suggestive of gastroesophageal reflux. Additionally, 22 asymptomatic healthy volunteers underwent pH monitoring. In patients with classic reflux symptoms and endoscopic esophagitis, a mean of 5.41 minutes/hour of reflux below pH 4 was found compared to 0.70 minutes/hour in controls (p less than 0.0001). The mean number and duration of reflux events in this group were 1.51 events/hour and 4.0 minutes/event, compared with 0.31 events/hour and 2.26 minutes/event in volunteers (p less than 0.001, p less than 0.01). A new system for ambulatory esophageal pH monitoring is presented using a pH-sensitive radiotelemetry pill or a pH probe and computerized methods for ambulatory data collection, analysis, and storage. An overall sensitivity of 76% was obtained with a 91% selectivity for detection of acid reflux in 51 patients having classic symptoms of gastroesophageal reflux. Ambulatory pH monitoring was positive for acid reflux in seven of 11 patients with normal endoscopic findings. Conversely, eight of 12 patients with normal pH monitoring had endoscopic esophagitis. In 19 patients presenting with atypical symptoms or previous gastric surgery, endoscopic findings were normal in 15. Nine of these 15 were identified as acid refluxers by pH monitoring. A combined approach using both pH monitoring and endoscopy is warranted for maximal detection and quantification of disease. A clear clinical role for pH monitoring is seen in the early diagnosis of acid reflux, particularly in patients having normal endoscopic findings with nonspecific gastrointestinal complaints or previous gastric operations.

Adult↗

Enhancement of the local inflammatory response to bacterial infection by muramyl dipeptide.

The effect of the synthetic immuno-adjuvant compound, muramyl dipeptide (MDP), upon the local inflammatory response to experimental bacterial infection was assessed by histological examination. Within 24 h of the insertion of a bacteria-laden suture into the medial thigh musculature of mice treated with either MDP or placebo, an enhanced degree of polymorphonuclear leucocyte infiltration in the muscle around the suture was observed in the MDP-treated animals. The inflammatory response around a sterile suture was less intense in both treatment groups and specific correlation between the degree of local inflammation and the extent of bacteraemia developing in either group of animals was not noted. The extent of bacteraemia developing in either group of animals was not noted. The previously observed protection conferred by MDP against the local impact of bacterial challenge appears to be mediated in part by enhancement of the acute local inflammatory response.

Acetylmuramyl-Alanyl-Isoglutamine↗

Time course adaptations in cardiac and skeletal muscle to different running programs.

The effects of chronic "steady-state" and high-speed interval running were investigated on time-course changes in certain biochemical properties of cardiac and skeletal muscle fiber types of rats. Nine weeks of the interval program resulted in significant increased (15%) in both cardiac enlargement and ATPase activity of myofibrils; whereas increases in these parameters were only transient and not significant at the termination of the program involving steady-state running. Neither program induced appreciable alterations in citrate synthase and phosphofructokinase activity in cardiac muscle. In fast-twitch white fibers, "steady-state" training induced only a transient 45% increase in citrate synthase activity in contrast to a progressive twofold change with interval training. Both programs resulted in similar increases (45-50%) in citrate synthase activity in fast-twitch and slow-twitch red fibers. However, the patterns of increase for both fiber types differed between the two programs. These findings suggest that training programs incorporating elements of both "steady-state" incline and high-speed interval running can potentially induce respiratory enzyme adaptations in the greatest spectrum of rodent skeletal muscle fibers in addition to inducing adaptations to enhance contractile potential in cardiac muscle.

Adenosine Triphosphatases↗

Effect of functional overload on enzyme levels in different types of skeletal muscle.

The effects of bilateral functional overload on enzyme changes in fast-twitch plantaris muscles were studied on different groups of rats: 1) normal-control; 2) normal-exercise; 3) overload-control; and 4) overload-exercise. Overload was accomplished by surgical elimination of synergists. Exercising groups walked up a 65% grade, 3 m/min, 2 h/day. Peak muscle enlargement of the overload groups was reached after 5 wk. Citrate synthase, phosphofructokinase, and myofibril ATPase activities were consistantly depressed by approximately 30%, 40%, and 18%, respectively, in overload as compared to normal groups. Daily exercise prevented the decrease in only citrate synthase activity. Unilateral overload of medial gastrocnemius muscle indicated that both fast-twitch oxidative-glycogenolytic and fast-twitch glycogenolytic fiber types undergo enzyme changes in response to the functional stress. However, changes in the former were in closer agreement with the net changes seen in the plantaris than the latter. Soleus muscle responded to overload primarily with marked reductions in respiratory capacity. These findings suggest that certain enzyme systems are altered with functional overload in different fiber types. However, the alterations in certain enzyme systems may, in part, be independent of the process of hypertrophy.

Adenosine Triphosphatases↗

Enzymatic changes in hypertrophied fast-twitch skeletal muscle.

Fast-twitch plantaris muscles of female rats were subjected to unilateral compensatory overload, induced by partial excision of synergistic muscles. One group of rats remained sedentary whereas another was subjected to a supplemental program of treadmill exercise consisting of walking 3 m/min, 65% grade, 2 h/day, 5 days/week. Groups of rats were sacrificed after 1, 2, 4, and 8 weeks and their muscles were weighed and analyzed for protein, citrate synthase, phosphofructokinase (PFK) and myofibril ATPase. Absolute and relative (muscle weight/body weight) muscle weights were much greater in both overloaded groups as compared to contralateral controls. However, treadmill exercise also increased the absolute and relative muscle mass of control plantaris muscles in the exercising group as compared tonormal sedentary contralateral controls. Citrate synthase activity was decreased in overloaded, sedentary muscles as compared to contralateral controls, but after 8 weeks of exercise, it returned to normal levels. PFK was decreased in both sedentary and exercised overloaded muscles throughout the 8 week period. Myofibril ATPase showed a tendency to be reduced in sedentary, overloaded muscles, and was significantly reduced in overloaded, exercising muscles. These results collectively suggest that certain fibers of overloaded fast-patterns take on similar in certain aspects to that normally seen in differentiated slow-twitch muscle fibers.

Adenosine Triphosphatases↗

The use of ERCP in the management of common bile duct stones in patients undergoing laparoscopic cholecystectomy.

The purpose of this study was to evaluate the indications and results of endoscopic retrograde cholangiopancreatography (ERCP) for gallstone disease since the advent of laparoscopic cholecystectomy. In our personal series of 410 consecutive cases of laparoscopic cholecystectomy, we found 17 common bile duct (CBD) stones; seven were identified by preop ERCP, nine at laparoscopy by intraoperative cholangiography, and one postop by ERCP. We have performed preop ERCP in 21 patients (5.1%); CBD stones were found in seven. Our indications for preop ERCP were elevated liver function tests, dilatation of the common duct by ultrasound, or a history of jaundice/pancreatitis, and all stones were successfully removed by endoscopic sphincterotomy. At laparoscopic cholecystectomy nine patients were found to have stones; one was treated with laparoscopic methods, four with open CBD exploration, and four by postop endoscopic sphinecterotomy. Post-laparoscopic cholecystectomy, five patients underwent ERCP for pain or increased liver function tests suggestive of common duct stones. One of the five was found to have stones and these were successfully removed by endoscopic sphincterotomy. ERCP is very useful as a diagnostic and therapeutic modality in laparoscopic cholecystectomy patients with suspected CBD stones. Elevated liver function tests and dilated CBD by ultrasound are the most accurate predictors of stones. Endoscopic sphincterotomy is a more effective route, at present, for stone removal than a laparoscopic approach.

Adolescent↗