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Biomedical subjects

P Tibbs

Publications and source records attributed to P Tibbs.

18 recordsLinked to original sources

Effects of nitric oxide synthase inhibitors and a substrate, L-arginine, on the cardiac function of juvenile salmonid fish.

Control of cardiac function was investigated juvenile brown trout (Salmo trutta L.) and rainbow trout (Oncorhynchus mykiss Walbaum) using inhibitors of nitric oxide synthase (NOS), (L-NAME, NG-nitro-L-arginine and L-NMMA, NG-monomethyl-L-arginine) and a substrate of NOS (L-arginine). Salmonid alevins are excellent models for such studies since they are transparent, the beating heart is easily observed, diffusing distances are small, and they respond within a few seconds to exogenously administered chemicals. The response to inhibitors of NOS (L-NAME or L-NMMA) was tachycardia interpreted as vasoconstriction through lowered capacity for synthesis of NO. This could be reversed by addition of L-arginine and the subsequent bradycardia was explained as a vasodilation resulting from increased synthesis of NO. Blood flow into the heart is mainly via the vitelline vein and changes of flow resulting from constriction or dilation of this vessel may be probably major determinants of heart rate. The results provide evidence for the presence NOS in juvenile fish and indicate a physiological role for NO in cardiovascular control.

Animals↗

Altered gastric emptying in the head-injured patient: relationship to feeding intolerance.

Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full-rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 +/- 0.5 days vs. 13.7 +/- 3.2 days, p less than 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days). This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings.

Adolescent↗

Relationship between admission hyperglycemia and neurologic outcome of severely brain-injured patients.

Severe head injury is associated with a stress response that includes hyperglycemia, which has been shown to worsen outcome before or during cerebral ischemia. To better define the relationship between human head injury and hyperglycemia, glucose levels were followed in 59 consecutive brain-injured patients from hospital admission up to 18 days after injury. The patients who had the highest peak admission 24-hour serum glucose levels had the worse 18-day neurologic outcome (p = 0.01). Patients with peak 24-hour admission glucose levels greater than 200 mg/dL had a two-unit increase in Glasgow Coma Scale score while patients with admission peak 24-hour serum glucose levels less than or equal to 200 mg/dL had a four-unit increase in Glasgow Coma Scale score during the 18-day study period (p = 0.04). There was a significant relationship between 3-month and 1-year outcome and peak admission 24-hour serum glucose level (p = 0.02 and p = 0.02, respectively). Those patients with admission peak 24-hour serum glucose levels less than or equal to 200 mg/dL had a greater percentage of favorable outcome at 18 days, 3 months, and 1 year than those with admission peak 24-hour glucose levels greater than 200 mg/dL (p = 0.0007, p = 0.03, and p = 0.005, respectively). A significant relationship between admission peak 24-hour Glasgow Coma Scale score and 18-day, 3-month, and 1-year outcomes was found (p = 0.0001, p = 0.0002, and p = 0.0002, respectively). Patients with mean admission peak 24-hour Glasgow Coma Scale scores of 3.5, 6, and 10 had mean admission 24-hour peak serum glucose levels of 252 +/- 23.5, 219.1 +/- 19, and 185.8 +/- 21, respectively (p = 0.05). These relationships were not significantly altered when confounding variables such as the amount of glucose given over the initial 24-hour postinjury period, the presence of diabetes or multiple injuries, and whether patients were given steroids, dilantin, or insulin were statistically incorporated. These data suggest that admission hyperglycemia is a frequent component of the stress response to head injury, a significant indicator of severity of injury, and a significant predictor of outcome from head injury.

Analysis of Variance↗

Prophylactic parenteral antibiotics in clean neurosurgical procedures: a review.

Clean surgical procedures carry a risk of postoperative wound infection that is less than 5% in most hospitals. The use of prophylactic antibiotic agents in clean neurosurgical cases is controversial, and the neurosurgical literature through 1980 contains no controlled clinical trials to study its effectiveness in such cases. A report of 1732 consecutive procedures without a single postoperative wound infection in patients receiving systemic gentamicin, vancomycin, and streptomycin irrigation fluids is often quoted by neurosurgeons; however, these results have not yet been duplicated by others. Since 1980, there have been several controlled trials that support the use in clean neurosurgical cases of prophylactic antibiotics, including the vancomycin/gentamicin/streptomycin regimen and the first-generation cephalosporins. A report in 1986 of 1602 cases without a primary wound infection supports the use of a single perioperative dose of cefazolin. A review of causative organisms in postoperative wound infections demonstrates the preponderance of Gram-positive pathogens. Therefore, when antibiotic prophylaxis is indicated, adequate Gram-positive bacterial coverage, including protection against Staphylococcus infection, is required. With consideration of the present data, the cost of antibiotic therapy, and the danger of drug toxicity, a short perioperative regimen of cefazolin as prophylaxis is preferred in clean neurosurgical cases.

Anti-Bacterial Agents↗

Clinical outcome of nosocomial pneumonia following imipenem/cilastatin therapy.

Eighteen patients in a neurosurgery intensive care unit who had nosocomial pneumonia and/or bacteremia were treated with imipenem/cilastatin. The 16 patients who were evaluable had pneumonia; 4 of these had concurrent bacteremia. Eleven patients had a satisfactory clinical response (69 percent) and all patients with positive blood cultures had the organism eradicated. There were 44 organisms isolated from the initial culture of bronchial secretion and 32 of these organisms were gram-negative bacilli (72.5 percent). One patient with pneumonia who initially had Pseudomonas aeruginosa sensitive to imipenem developed resistance during therapy. Adverse effects were minimal; one case of nausea occurred, which was thought to be related to a short infusion time. The most prominent laboratory abnormality was an increase in platelet count, seen in 50 percent of treated patients.

Adult↗

Effect of total parenteral nutrition upon intracranial pressure in severe head injury.

Animal investigations suggest that administration of hyperosmolar total parenteral nutrition (TPN) solutions may potentiate cerebral edema following head injury. Intravenous nutrition (TPN) is often required after head injury due to intolerance to enteral feeding (EN). This study evaluates the effect of TPN on intracranial pressure (ICP) measurements in severely brain-injured patients. Ninety-six severely brain-injured patients were randomly assigned to receive TPN or EN and were studied from hospital admission until 18 days postinjury. The TPN was started within 48 hours postinjury and the EN was started when tolerated. Peak daily ICP was not significantly different on admission and over time (overall mean +/- standard error of the mean 32.01 +/- 1.62 for TPN versus 32.5 +/- 1.25 for EN). Intracranial pressure was greater than 20 mm Hg in 75% of TPN patients and 73% of EN patients. Conventional therapy failed to control elevated ICP in 36% of TPN patients and 38% of EN patients. Of these patients, subsequent barbiturate therapy failed to control ICP in 56% of TPN patients and 64% of EN patients. Serum osmolality was not significantly different between groups at admission or over the course of the study. The TPN group tended to have higher mean serum glucose levels for the first 13 days postinjury, while the EN group had a higher mean serum glucose content thereafter, but these differences were not statistically significant. This study shows that TPN can be given safely to the severely brain-injured patient without causing serum hyperosmolality or affecting ICP levels or ICP therapy.

Brain Injuries↗

The effect of nutritional support on outcome from severe head injury.

Fifty-one brain-injured patients with peak 24-hour admission Glasgow Coma Scale (GCS) scores of 4 to 10 were prospectively randomly assigned to receive total parenteral (TPN) or enteral (EN) nutrition. Patients were studied from hospital admission to 18 days postinjury. Outcome was assessed by the Glasgow Outcome Scale at 3 months, 6 months, and 1 year postinjury. The TPN group received a significantly higher cumulative mean intake of protein than the EN group (mean +/- standard error of the mean: 1.35 +/- 0.12 vs. 0.91 +/- 0.9 gm/kg/day; p = 0.004). Mean cumulative caloric balance was also significantly higher in the TPN than in the EN group (75.6% +/- 5.13% vs. 59% +/- 4.26%; p = 0.02). Nitrogen balance was significantly more negative in the EN group during the 1st week postinjury (p = 0.002). The incidence of pneumonia, urinary tract infections, septic shock, and infections was not significantly different between groups. Classic nutritional assessment parameters such as anergy screens, total lymphocyte counts, and albumin levels were not significantly different between groups. The 11 patients in the EN group who did not tolerate tube feedings for 1 week postinjury had a significantly higher incidence of septic shock (p = 0.008). The change over time in GCS scores between groups was significantly different, with the TPN group showing a mean four-point increase in GCS score compared with a three-point increase in the EN group (p = 0.02). At 3 months the TPN group had a significantly higher percentage of favorable outcomes (43.5% vs. 17.9%, respectively; p = 0.05). At 6 months, 43.5% of the TPN group had a favorable outcome while 32.1% of the EN group had a favorable outcome (p = 0.29). By 1 year, 47.8% of the TPN group and 32.1% of the EN group had a favorable outcome (p = 0.20). In conclusion, more calories and protein usually can be administered to acute brain injury patients via the TPN route than by EN feedings via nasogastric or nasoduodenal routes. Traditional parameters for nutritional assessment are not useful in studying the efficacy of nutritional support during the first 2 weeks after head injury. Neurological recovery from head injury occurs more rapidly in patients with better early nutritional support.

Craniocerebral Trauma↗

A clinical study with brain brachytherapy for malignant gliomas.

A clinical trial with neutron brachytherapy for malignant glioma is now in progress at the University of Kentucky Medical Center. In the initial three year period, 32 patients entered the study. There were 24 males and eight females, and the peak incidence was seen in the seventh decade. All patients underwent surgical resection of tumor followed by Cf-252 implantation and external radiotherapy. The implantation procedure was well tolerated by the patients and demonstrated a short-term benefit in survival of patients who were able to complete planned radiotherapy. Older patients had less tolerance to radiotherapy. The evaluation of the beneficial effects of Cf-252 brachytherapy will require patients who are able to tolerate the whole course of therapy.

Adult↗

Metabolic and nutritional sequelae in the non-steroid treated head injury patient.

Energy production, substrate oxidation, serum protein levels, and weight change were studied in 16 non-steroid treated patients with severe head injury. Patients were evaluated during an average of 31.3 days from hospital admission to discharge. The mean measured energy expenditure (MEE) was 1.40 +/- 0.5 times predicted energy expenditure. Caloric balance [calories received = calories expended] was achieved by the 2nd week. Despite caloric balance and the administration of at least 1.5 g of protein per kg of body weight per day, the mean nitrogen balance was negative. There was a positive nitrogen balance in only 2 patients. These patients received a mean of 1.43 times the MEE in total kilocalories and 2.3 g of protein per kg of body weight. Fat and protein oxidation exceeded protein and fat administration for 3 weeks postinjury. Albumin levels dropped from a mean of 3.09 +/- 0.2 on admission to 1.98 +/- 0.4 within 2 weeks. The initial retinol binding protein levels were within the normal range, and the levels increased over time. There was marked weight loss (mean, 15.6 +/- 5.9 lb). Head injury induces a profound traumatic response identified by increased energy expenditure, a negative nitrogen balance, weight loss, hypoalbuminemia, and altered substrate oxidation. This response seems to be caused by the head injury alone and is not due to the administration of corticosteroids.

Adolescent↗

Cerebellar glioblastoma in childhood.

Cerebellar glioblastoma multiforme in childhood is extremely rare. Only ten such cases have been reported to date. Although treatment results are reported to be extremely poor, complete tumor clearance was achieved in a patient treated with superfractionated radiotherapy. She received high dose postoperative radiotherapy using a three times per day technique and is disease-free for more than three years posttherapy. This suggests that improved tumor response can be obtained by high dose postoperative radiotherapy using a modified fractionation technique.

Adolescent↗

Intracerebral neutron brachytherapy for hemispheric glioblastoma multiforme. A pilot study.

The University of Kentucky Brain Tumor Study and Research Group has developed a new treatment protocol of interstitial brain brachytherapy using Californium-252 neutron source implantation in 1980. Only patients with malignant gliomas were eligible for this pilot study. Nine patients entered the Phase I trial of the protocol study between November 1980 and October 1981. According to the design of the protocol, all patients who had a verified histologic diagnosis of glioblastoma multiforme underwent postoperative intracerebral Cf-252 neutron source implantation, followed by 6 000 cGy of external photon beam irradiation. The purpose of this pilot study was to test the feasibility of interstitial Cf-252 neutron source implantation and only one implant afterloading applicator was used for brachytherapy. The implant applicator was placed in the center of tumor and the procedure was performed under CT guidance. In the assessment of the procedure, Karnofsky functional performance status, intellectual status, neurological examination, CT scans, and complications were used. All patients tolerated the procedure well and no serious complications were encountered. Despite the quality of these early treatments, there was some evidence of short-term benefit in duration of survival of the patients. We believe that further technical improvement to achieve an adequate isodose distribution to cover the tumor volume might result in longer duration improvement in survival.

Aged↗

CT and MR for brain tumor implant therapy using CF-252 neutrons.

Magnetic resonance (MR) imaging of the brain allows very effective localization of tumor in brain, visualization of brain reaction to tumor, peritumoral edema, as well as destruction of normal anatomy and spread of tumor. MR readily imaged the brain in multiple views allowing three dimensional (3D) evaluation and more precise localization of tumor in the depths of the brain. It also assessed the extent of tumor infiltration away from the primary site. In an ongoing study of Cf-252 neutron brachytherapy of hemispheric malignant gliomas of the brain, we have found that the extent of tumor and the planning of the placement of multiple applicators in the brain for implant therapy was facilitated by both CT and MR scanning, but MR allowed better 3D localization, assessment of response and follow-up of tumor response. MR gave additional and different types of information about the tumor than CT scanning based upon proton distribution which greatly aided planning of tumor implant therapy and understanding of patterns of tumor response and recurrence after therapy.

Adult↗

Implantation of brain tumors with Cf-252. Use of computed tomography and magnetic resonance imaging to guide insertion and evaluate response.

Magnetic resonance imaging (MR) was evaluated as a guide to planning and follow-up of Cf-252 neutron brachytherapy in 8 patients with malignant glioma of the cerebral hemispheres. A combination of sagittal, transverse, and coronal views allowed three-dimensional assessment of the dimensions and extent of tumor; by comparison, CT scans delineated the tumor less sharply, multiple views were not routinely obtained, and the reconstructed sagittal images were inadequate. Both techniques were complementary in enabling accurate tumor localization as well as separating enhanced zones from central avascular regions and tumor from edema. However, MR images provided more detail than serial CT scans, making MR the preferred method of follow-up.

Brachytherapy↗

Interstitial 252Cf neutron therapy for glioblastoma multiforme.

252Cf brachytherapy has been combined with whole brain photon beam therapy to 6000 rads in 5-7 weeks. In early phase I studies, all patients selected for study tolerated the procedure and the subsequent photon beam therapy. All showed improvement in performance status and decreased tumor size by CT scan evaluation, but it became clear that these tumors are of large size and bulk, produce marked adjacent brain edema, and require individualized implant therapy as well as high-dose external beam irradiation if response is to occur.

Brachytherapy↗

Work in progress: 252Cf neutron brachytherapy for hemispheric malignant glioma.

It has been shown that 252Cf neutron brachytherapy of hemispheric malignant glioma can be readily carried out and may be combined with external, whole brain photon beam therapy of 6,000 rad (60 Gy) administered over a five-week to seven-week period. The ten patients who were studied tolerated both procedures well. There was improvement in performance status, and a decrease in tumor size was observed upon computed tomographic scanning.

Aged↗

Comparison of urinary urea nitrogen excretion and measured energy expenditure in spinal cord injury and nonsteroid-treated severe head trauma patients.

Severe head trauma patients (HT) exhibit markedly elevated energy expenditure and 24-hr urinary urea nitrogen excretion (UUN) values. The objective of this study was to compare seven spinal cord injured patients (SCI) to seven HT for changes in UUN and measured energy expenditure (MEE) over the first 18 days following injury. Energy expenditure was measured by indirect calorimetry and compared to values predicted by the Harris Benedict Equation (PEE). There were six quadriplegics and one paraplegic in the SCI group. HT patients had peak Glasgow Coma Scale scores of 3 to 10 for the first 24 hr postinjury. Patients were studied prospectively and matched for age, sex, and admitting weight Week 1 following the injury, SCI had mean UUN values of 0.18 +/- 0.04 g/kg/day vs 0.18 +/- 0.01 for HT patients. The mean MEE/PEE ratio was 0.56 for the SCI and 1.4 for HT (p less than 0.01). Over the entire study period the mean UUN value for SCI was 0.23 +/- 0.03 g/kg vs 0.21 +/- 0.01 for HT. The mean MEE/PEE ratio for SCI was 0.94 while HT remained elevated at 1.5 (p less than 0.05). Although the UUN was comparable in SCI vs HT, there was a significant difference in MEE/PEE between the groups. The elevation in UUN observed in SCI is not due to a hypermetabolic state. This suggests that different mechanisms promote the increased nitrogen excretion observed in these two populations.

Acute Disease↗