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Biomedical subjects

R Knox

Publications and source records attributed to R Knox.

At least 19 recordsLinked to original sources

A five-year experience with severe injuries in elderly patients.

Recent reports of injury in elderly patients document that aggressive care is justified. Our experience indicates that geriatric injury differs from that of other trauma patients. All patients entered into a large urban trauma center registry over a five-year period were analyzed. Variables reviewed included demographics, trauma indices, mechanism of injury, mean number of hospital days, and morbidity and mortality for patients under 60 years old and for geriatric patients defined as those aged 60 and above. There were 3,064 patients in the reviewed group, of whom 243 qualified for geriatric analysis. Blunt injuries in males were the most typical scenario. Failure to use safety belts and alcohol intoxication persist into the geriatric age group (83% and 13%, respectively). Trauma indices including Injury Severity Score (ISS) were slightly greater in the geriatric group (27 versus 23) as compared to younger patients; plus geriatric patients tolerated head injury less well (GCS in those who died 6.7 versus 4.6, respectively; p < 0.001). Mortality in the geriatric group was 31% while being 17.1% in the younger group (p < 0.005). Days in the hospital were 20 for the geriatric compared to 13 for the younger group (p < 0.025). Infections and chest complications were twice as common in the elderly and dysrhythmias were five times more frequent. Elderly patients constitute 8% of the trauma population and suffer a magnitude of injury at least comparable to the general population. Their mortality is approximately 50% above the population as a whole and morbidity twice as common, accounting for the prolonged hospital stay.

Accidents, Traffic

Catalytic properties of NAD(P)H:quinone acceptor oxidoreductase: study involving mouse, rat, human, and mouse-rat chimeric enzymes.

NAD(P):quinone acceptor oxidoreductase (quinone reductase) (DT-diaphorase, EC 1.6.99.2) is involved in the process of reductive activation of cytotoxic antitumor quinones and nitrobenzenes. In this study, we initially examined the relative abilities of mouse, rat, and human quinone reductases to reduce two prodrugs, CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] and EO9 [5-(1-aziridinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1- methyl-1H-indole-4,7-dione]. By using Escherichia coli-expressed quinone reductases and evaluating them under identical conditions, we confirmed previous finding showing that the human enzyme is not as effective as the rat enzyme in reducing CB 1954 and EO9, although the two enzymes have similar NAD(P)H-menadione reductase activities. Interestingly, although the amino acid sequence of mouse quinone reductase is more homologous to that of the rat enzyme, we found that the mouse enzyme behaves similarly to the human enzyme in its ability to reduce these compounds and to generate drug-induced DNA damage. To determine the region of quinone reductase that is responsible for the catalytic differences, two mouse-rat chimeric enzymes were generated. MR-P, a chimeric enzyme that has mouse amino-terminal and rat carboxy-terminal segments of quinone reductase, was shown to have catalytic properties resembling those of rat quinone reductase, and RM-P, a chimeric enzyme that has rat amino-terminal and mouse carboxyl-terminal segments of quinone reductase, was shown to have catalytic properties resembling those of mouse quinone reductase. In addition, MR-P and RM-P were found to be inhibited by flavones with Ki values similar to those for rat and mouse quinone reductases, respectively. Based on these results, we propose that the carboxyl-terminal portion of the enzyme plays an important role in the reduction of cytotoxic drugs and the binding of flavones.

Amino Acid Sequence

Fibrinogen and the albumin-globulin ratio in recurrent stroke.

BACKGROUND AND PURPOSE: In following patients initially recruited for a cross-sectional study of blood viscosity in ischemic cerebrovascular disease, it was noted that those having a low albumin-globulin ratio appeared to experience the majority of subsequent vascular events. Accordingly, a prospective study in which subjects were assigned to a high or low albumin-globulin cohort was undertaken to examine the relation between a low albumin-globulin ratio, the presence of clinical risk factors for stroke, and the occurrence of subsequent stroke, myocardial infarction, or vascular death. METHODS: Three groups of subjects were followed for an average of 1.5 +/- 0.8 years to ascertain vascular end points. Group 1 consisted of 126 patients with acute ischemic stroke; group 2 included 109 subjects matched with group 1 for age, medications, and recognized clinical risk factors for stroke; and group 3 was composed of 84 healthy volunteers, matched for age with groups 1 and 2. The median albumin-globulin ratio for group 1 at enrollment, 1.45, was used to dichotomize patients into two cohorts: all subjects with an albumin-globulin ratio of 1.45 or less were assigned to the "low" albumin-globulin cohort; those whose ratio was greater than 1.45 were assigned to the "high" albumin-globulin cohort. The occurrence of vascular end points was verified during subsequent hospitalizations and outpatient clinic visits and by telephone interviews of patients and providers. RESULTS: A total of 51 vascular events occurred, including 39 in group 1, 8 in group 2, and 4 in group 3. Subjects in either group 1 or 2 who were in the low albumin-globulin cohort had at least double the risk for a subsequent vascular event compared with their counterparts in the high albumin-globulin cohort (P < .01 and P < .03, respectively). In comparison with the high albumin-globulin cohort, significantly more patients in the low albumin-globulin cohort in group 1 had a history of prior stroke (P < .03). When groups 1 and 2 were combined, both a low albumin-globulin ratio and diabetes had a significant independent association with increased risk for subsequent vascular events in a Cox proportional-hazards model (P < .01 and P < .03, respectively). CONCLUSIONS: The results of this study indicate that significantly increased risk for subsequent vascular events in stroke patients and in subjects with clinical risk factors for stroke is associated with a shift in the concentrations of blood proteins to a prothrombotic environment characterized by lower levels of albumin and an increased concentration of globulins and fibrinogen.

Aged

Placement of hydroxyapatite-coated endosseous implants in fresh extraction sites: a case report.

This case illustrates the use of the principles of guided tissue regeneration to achieve osseointegration of an endosseous dental implant. One implant was placed immediately, with hydroxyapatite and a barrier membrane, in an extraction site, while another was placed in a healed site. Eighteen months postinsertion, the implant placed in the extraction socket exhibited better maintenance of crestal height than did the implant inserted in the healed site.

Adult

Steroid use is associated with pneumonia in pediatric chest trauma.

A review of pediatric trauma focused on pediatric chest injuries was performed at a trauma center specializing in neurologic trauma. Eighty of 342 (23%) pediatric trauma patients admitted to the center had chest injuries. Age, gender, mechanism of injury, magnitude of injury, incidence of pulmonary infection, chest tube usage, endotracheal intubation, steroid or antibiotic usage, morbidity, and mortality data were reviewed. Sixteen of 78 children (20%) with chest injuries developed pulmonary infections and were compared with the noninfected group. Patients with pneumonia had a higher morbidity with significantly longer mean hospital stay (43.0 vs. 12.7 days; p = 0.001), duration of intubation (8.4 vs. 1.5 days; p = 0.001), and total days with chest tubes, (2.2 vs. 1.4 days; p = 0.02). Pneumonia was significantly associated with longer mean duration of steroid usage (6.4 vs. 0.8 days; p = 0.0001). Duration of steroid administration for the treatment of concomitant brain injury was a significant independent risk factor for the occurrence of pneumonia.

Adolescent

Effect of fat pre-feeding on bile flow and composition in the rat.

Studies were conducted in rats to determine if the increase in lymph triacylglycerol output on pre-feeding a 20% glyceryltrioleate diet (Mansbach, C.M., II and Arnold, A. (1986) Am. J. Physiol. 251, G263-269) was due to an increase in phosphatidylcholine output into bile. Rats who were fed chow or pre-fed the 20% fat diet were equipped with biliary and duodenal cannulas and infused with glucose-saline while bile was collected hourly. The next day a taurocholate-glyceryltrioleate infusion was given and bile collected for 5 h. Bile flow, bile acid, phosphatidylcholine and cholesterol output were greater in the chow fed group than controls during the 6 h of the glucose saline period. Outputs were low overnight. During the taurocholate-glyceryltrioleate infusion, bile flow, bile acid, phosphatidylcholine and cholesterol output were all greater in the fat pre-fed group than the chow fed controls. We conclude that fat pre-feeding profoundly influences biliary composition and flow. The 2-fold increase in biliary phosphatidylcholine output during duodenal lipid infusion offers a potential explanation for the increased delivery of triacylglycerol into the lymph in rats on a similar fat pre-feeding program.

Animals

Chronic blood hyperviscosity in subjects with acute stroke, transient ischemic attack, and risk factors for stroke.

The origin and significance of blood hyperviscosity in subjects with acute stroke has been controversial. It has been argued that viscous abnormalities simply reflect either elevated hematocrit or an acute-phase response to the stroke itself. To address these issues, we measured the factors that determine blood viscosity in a cross-sectional study of 430 subjects, including 135 with acute stroke, 89 with acute transient ischemic attacks of the brain, 115 with recognized risk factors for stroke, and 91 healthy controls. The at-risk group was balanced with the acute stroke group for types of risk factors and medication usage, and all four groups were balanced for age. The viscosity of whole blood at low rates of shear and the plasma viscosity were significantly elevated in both groups with cerebrovascular symptoms and in the at-risk group compared with the healthy controls. The severity of hyperviscosity was stroke group greater than transient ischemic attack group greater than at-risk group greater than healthy controls. Increased viscosity of whole blood was associated with an elevated plasma fibrinogen concentration and with a decreased albumin/globulin ratio. This study provides evidence that blood hyperviscosity is present not only in subjects with acute brain infarction, but also in those with risk factors for stroke, and that these abnormalities are, to a considerable degree, chronic.

Acute Disease

Heterotopic lingual brain in the newborn.

Heterotopic brain is a rare entity. Histologically, this lesion resembles mature brain and often contains specialized tissues similar to choroid plexus or glia. Specialized neural stains are necessary to differentiate this rare anomaly from other tumors or conditions found in the head and neck. The differential diagnosis includes squamous cell carcinoma, granular cell tumor, hemangioma, lymphangioma, thyroglossal duct cyst, dermoid cyst, hamartoma, rhabdomyosarcoma, and teratoma. We describe a newborn with heterotopic brain tissue occurring on the dorsum of the tongue. We found only one other description of this developmental aberration in the English literature. Our patient was successfully treated with carbon dioxide laser excision of the mass. There has been no evidence of complication or recurrence after one year of follow-up.

Brain

Effect of helicopter transport of trauma victims on survival in an urban trauma center.

This paper reports a retrospective analysis of patients with serious yet substantially survivable injuries represented by ISS scores from 20 to 39 and whether or not survival was influenced by the use of helicopters. A review of 606 of these patients with blunt trauma was performed for the period from 1983 through 1986. When the group was evaluated there were 451 patients in the ISS cohort of 20-29 and 155 in the 30-39 group. The mean age was 30.5 years and 76% were males. A total of 259 patients were transported by ambulance and 347 by helicopter. Characteristics of the two groups were similar. The mean TS was 12.7 for ambulance and 12.1 for helicopter patients. Mean GCS was 10.4 in the ambulance group and 9.6 for helicopter patients. Overall the mortality for ambulance transported patients was 13% compared to 18% for the helicopter group. We conclude that there is no survival advantage in the helicopter transported group in an urban area with a sophisticated prehospital care system. Patients of rural origin deserve further study.

Adult

Opioid receptor subtypes in the rat spinal cord: electrophysiological studies with mu- and delta-opioid receptor agonists in the control of nociception.

We have compared the ability of selective mu- and delta-opiate agonists to modulate nociceptive transmission at the level of the rat dorsal horn using electrophysiological approaches. Single-unit extracellular recordings were made from neurones in the lumbar dorsal horn of the intact rat under halothane anaesthesia. Neurones could be activated by both A- and C-fibre electrical stimulation (and by natural innocuous and noxious stimuli). Agonists were applied directly onto the cord in a volume of 50 microliters. The intrathecal administration of 3 agonists, Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO) (mu-selective) (2 X 10(-3)-10 nmol) Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) (mu/delta) (7 X 10(-4)-70 nmol), and cyclic Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE) (delta) (2 X 10(-2)-100 nmol) produced dose-dependent inhibitions of C-fibre-evoked neuronal activity whilst A-fibre activity was relatively unchanged. DAGO produced near-maximal inhibitions which could be completely reversed by naloxone (1.5 nmol) whilst DPDPE causes less marked inhibitions which could only be partially reversed by naloxone (1.5-13.5 nmol). DTLET produced effects intermediate to those of DAGO and DPDPE. The results suggest that both mu- and delta-opioid receptors can modulate the transmission of nociceptive information in the rat spinal cord.

Animals

Management of colovesical fistula.

The clinical presentation and management of 24 patients treated for colovesical fistula were reviewed. It is concluded that an aggressive investigative approach in the management of patients with suspected colovesical fistula is rewarding. Cystoscopy and barium enema appear to be the most useful investigative tools. Once found the fistulae should be managed surgically. Radical excision of the sigmoid colon with primary anastomosis is the treatment of choice and is accompanied by no mortality and a very low complication rate.

Adult

Comparison of primary and secondary treatment in squamous oral cancer.

A popular rule of thumb has often prevailed in treating oral cancer: Try one modality first; if it fails, try the other--the chance for cure will still be good. To study this dogma, a group of 160 consecutive patients with oral cavity squamous carcinoma were reviewed. A hypothesis was formed: secondary treatment for recurrent cancer, whether surgery after radiation failure or vice versa, would salvage essentially as many patients as primary treatment, say within 15%. Results show a large difference in success rates between first and second treatments when all stages are considered together, a difference well over 15 percentage points. Regarding each stage separately, the largest difference occurs in stage II (28 percentage points); other stages exceed 15 point differences. No significant differences in successful salvage occur between "home" failures and "elsewhere" failures. Local recurrence was a major cause of failure in both groups (55%). We conclude that recurrence of oral squamous cancer after first treatment markedly reduces patients' chance for cure.

Aged