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Biomedical subjects

D J Cole

Publications and source records attributed to D J Cole.

At least 19 recordsLinked to original sources
PubMed1992

Melanoma of the external ear.

Management of melanoma of the external ear is controversial. Thirty-one patients treated for this disease were identified at our institution between January 1, 1974 and December 31, 1989. Follow-up was an average of 7.12 years (range 1-15). Local therapy performed included 16 wedge resections, 3 split thickness skin grafts after excision to the perichondrium, 10 partial and 2 total amputations. There were two local recurrences, four metachronous cervical metastases, and four distant metastases. Three elective and five therapeutic neck dissections were performed. Survivors at 1, 5, and 10 years were 93, 77, and 47%, respectively. There was no relationship between DNA ploidy, local surgical therapy, and eventual recurrence. Clinical stage and tumor thickness demonstrated a statistically significant correlation with likelihood of recurrence (P = .02 and .05). There is no evidence that melanoma of the ear has a poorer prognosis or different prognostic factors than melanoma at other cutaneous sites. In selected cases, local disease can be controlled by excision and skin graft rather than the more aggressive current procedures.

Adult↗
PubMed1992

Eicosanoid production in the caudate nucleus and dorsal hippocampus after forebrain ischemia: a microdialysis study.

Thromboxane (Tx)B2 and 6-keto-prostaglandin (6-keto-PG) F1 alpha formation in the hippocampus and caudate nucleus were evaluated by microdialysis during and following forebrain ischemia. Spontaneously hypertensive rats were subjected to bilateral carotid artery occlusion with simultaneous hypotension for 8, 14, or 20 min. Dialysate was collected during the ischemic interval and during the reperfusion period. TxB2 and 6-keto-PGF1 alpha levels were measured by radioimmunoassay. In both structures, TxB2 production increased significantly during the reperfusion period in all three ischemic groups. By contrast, increased 6-keto-PGF1 alpha elaboration was observed after only the longest ischemic duration. While TxB2 levels gradually decreased during the 3-h reperfusion period in all groups, the levels in the group subjected to 8 min of ischemia returned to control values most rapidly. A relationship between the duration of ischemia and TxB2 production was therefore evident. 6-Keto-PGF1 alpha levels increased in only the group subjected to 20 min of ischemia and, by contrast to the pattern of TxB2 change, 6-keto-PGF1 alpha levels remained elevated throughout the reperfusion period. During reperfusion, the ratio of TxB2 to 6-keto-PGF1 alpha increased substantially versus the preischemic period in both structures. The data demonstrate that eicosanoid elaboration following cerebral ischemia can be evaluated by the microdialysis technique. In addition, they indicate that the thresholds (duration of ischemia) for the postischemic production and the temporal profiles of TxB2 and 6-keto-PGF1 alpha in the caudate and hippocampus differ. They also demonstrate that there is regional heterogeneity in the patterns of eicosanoid elaboration after forebrain ischemia.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross-linked hemoglobin on CBF.

Hemodilution has had limited success as a treatment of cerebral ischemia. When using a nonoxygen binding fluid, the therapeutic efficacy of hemodilution-induced increases in CBF are offset by concomitant decreases in oxygen content. The effect of hemodilution, with diaspirin alpha-alpha cross-linked hemoglobin (DCLHb), on CBF during middle cerebral artery occlusion was assessed. Rats were hemodiluted to one of the following hematocrits (Hct): (a) 44/Hct, (b) 37/Hct, (c) 30/Hct, (d) 23/Hct, (e) 16/Hct, or (f) 9/Hct. After 10 min of ischemia, CBF was determined with 14C-iodoantipyrine. Coronal brain sections were evaluated for areas with a CBF of 0-10 and 11-20 ml 100 g-1 min-1. In addition, oxygen delivery was calculated. In the center of the ischemic zone, both areas of low CBF were less in the 30/Hct, 23/Hct, and 16/Hct groups compared with the 44/Hct and 37/Hct groups; and both areas were less in the 9/Hct group compared with the other five groups (p < 0.05). For the hemisphere contralateral to occlusion, there was a direct correlation between hematocrit and oxygen delivery. However, for the hemisphere ipsilateral to occlusion, oxygen delivery increased as hematocrit decreased (44/Hct, 8.6 +/- 0.3 vs. 9/Hct, 13.6 +/- 0.4 [mean +/- SD, ml 100 g-1 min-1]). The results of this study support a hypothesis that hemodilution with DCLHb decreases the extent of focal cerebral ischemia.

Animals↗
PubMed1992

Focal cerebral ischemia in rats: effects of induced hypertension, during reperfusion, on CBF.

The effect of phenylephrine-induced hypertension on CBF was investigated after 120 min of middle cerebral artery occlusion in rats. Blood pressure was manipulated by one of the following schedules during a 90-min period of reperfusion: 90/NORM, 90 min of normotensive reperfusion; 90/HTN, 90 min of hypertensive reperfusion (MABP increased by 30 mm Hg); or 15/HTN, the 90-min period of reperfusion was divided into 30 min of normotension, followed by 15 min of hypertension and 45 min of normotension. At the end of reperfusion, 100 microCi kg-1 of [14C]iodoantipyrine was given and an autoradiographic analysis of CBF performed. In the coronal brain section at the center of middle cerebral artery distribution, the area (percentage of hemisphere, mean +/- SD) with a CBF of 0-20 or 21-40 ml 100 g-1 min-1 was less (p less than 0.05) in the 15/HTN group (1 +/- 2 and 5 +/- 3%, respectively) versus the 90/HTN group (12 +/- 4 and 10 +/- 4%), which was in turn less than in the 90/NORM group (18 +/- 5 and 22 +/- 6%). These data are consistent with the hypothesis that during reperfusion a short interval of hypertension effectively augments CBF via an abrupt opening of collapsed vessels and that a more sustained interval of hypertension conveys no added benefit.

Animals↗
PubMed1992

Evaluation of inert markers for the determination of ileal and faecal apparent digestibility values in the pig.

A series of experiments was designed to evaluate inert markers employed in studies of ileal and faecal apparent digestibilities of nitrogen and amino acids in pigs fitted with simple 'T' piece cannulas. Trial 1 assessed the palatability of diets containing (a) 5 g chromic oxide/kg, (b) 1 and (c) 5 g titanium dioxide/kg at two levels of feeding. The results indicated that there were slight problems in terms of period of feed consumption associated with diets (a) and (c), but that these effects were transitory and disappeared following acclimatization, although higher levels of feeding may compound the problem. Trial 2 estimated N balance, faecal apparent digestibility of amino acids as determined by both total collection and ratio of markers, ileal apparent digestibility of amino acids and recovery of markers using diets containing (a) 1 and (b) 5 g Cr2O3/kg, (c) 1 and (d) 5 g TiO2/kg. An additional assessment of acid-insoluble lignin present within the diet was also undertaken. Cr2O3 was associated with the lowest recovery, whilst calculations based on TiO2 gave lower standard errors. Trial 3 examined diurnal variation in digesta sampling and its effect on faecal apparent digestibility of N and amino acids. There were no evident effects. In general, it was concluded that the most appropriate marker to use in studies of this nature was TiO2 at a rate of 1 g/kg.

Amino Acids↗
PubMed1992

A comparison of the cerebral protective effects of isoflurane and mild hypothermia in a model of incomplete forebrain ischemia in the rat.

The present study was undertaken to examine the cerebral protective properties attributed to isoflurane and at the same time to compare its protective effects with those of mild hypothermia (temperature reduction by 3 degrees C). Twenty-one fasted Wistar-Kyoto rats were assigned to one of three groups (n = 7); 1.3 MAC (end-tidal) isoflurane-normothermia (pericranial temperature 38.0 degrees C), 1.3 MAC halothane-normothermia, and 1.3 MAC halothane-hypothermia (pericranial temperature 35.0 degrees C during ischemia). In each animal the trachea was intubated and the lungs were mechanically ventilated. Each animal was subjected to temporary incomplete forebrain ischemia induced by 10 min of bilateral carotid artery occlusion with simultaneous hypotension (mean arterial pressure 35 mmHg) induced by trimetaphan and blood withdrawal. After a 3-day survival period, perfusion-fixation was performed, and two blinded observers assessed histopathologic injury according to a four-point scale (0 = no damage; 1 = less than 10% of neurons damaged; 2 = 10-50% damaged; and 3 = greater than 50% damaged). The assessment was performed at two points in the rostrocaudal axis chosen to permit evaluation of regions with varying levels of ischemic damage. In the rostral sections, in the isoflurane- and halothane-normothermia groups, moderate to severe injury was observed in striatum, cerebral cortex, hippocampus (CA1 and CA3 areas), and reticular nucleus of the thalamus (e.g., the median scores for the CA1 area were 3 in both the halothane-hypothermia and the isoflurane-normothermia groups), and there were no differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The reversibility of death.

The ordinary concept of death is analysed and compared with revisionary medical definitions, especially those based on irreversible loss of brain function. Prior critics of revisionary definitions have focused on the locus, the brain; I am concerned with the irreversibility condition. I argue that 1) the irreversibility condition is ambiguous, 2) it has unacceptable epistemic and other consequences on any plausible construal, and 3) irreversibility is not part of the ordinary concept of death. I conclude that recent medical definitions seek illegitimately to obtain the certainty of a weak construal of 'irreversible' along with the freedom from moral obligation of the strong construal.

Attitude to Death↗
PubMed1992

A pilot study of accelerated fractionation in the radiotherapy of invasive carcinoma of the bladder.

24 patients with muscle invasive carcinoma of the bladder were treated in a pilot study of twice daily fractionation at radiation doses of 1.8-2.0 Gy per fraction to total doses of 54-64 Gy to the bladder and 39.6-44 Gy to the whole pelvis. The treatment aim was to give 32 fractions in 22 days. The interfraction interval was a minimum of 6 h. The principle objective was to record acute and late tolerance, but local control and survival data is also presented. Acute radiation morbidity was scored according to the RTOG system. Grade 2 large bowel effects were seen in 52% of patients, Grade 3 effects in 26% and there was one Grade 4 and one Grade 5 effect. The mean duration of effect was 4.5 weeks although the more severe reactions were also more protracted. Grade 2 urinary effects occurred in 30% and Grade 3 in 17% of patients. The mean duration of effect was 7.2 weeks. There were no Grade 4 or 5 acute urinary effects. Late radiation morbidity was scored according to the EORTC/RTOG system and was assessable in 16 cases who survived more than 6 months. There were two cases (12%) of Grade 1 bowel toxicity, two cases of Grade 1 and three of Grade 2 urinary toxicity. There were no cases of late skin effects. Actuarial analysis at 2 years shows a local control probability of 56% and survival probability of 35%.

Acute Disease↗
PubMed1992

Temporary cerebral ischemia. Effects of pentastarch or albumin on reperfusion injury.

Recent investigations have proposed that, after temporary ischemia, pentastarch may reduce microvascular permeability and reperfusion injury. However, this hypothesis has not been tested in the brain. Accordingly, after 180 min of temporary middle cerebral artery occlusion, the effect of pentastarch or albumin on blood-brain barrier permeability and cerebral injury was investigated in isoflurane-anesthetized rats. One of the following was maintained for the final 60 min of occlusion and throughout reperfusion: control-hematocrit was not manipulated; pentastarch-hematocrit was decreased to approximately 30% with pentastarch; or albumin-hematocrit was decreased (approximately 30%) with albumin. Part A (n = 21): 30 min of reperfusion was allowed, and blood-brain barrier permeability was determined with the indicator dye Evans Blue. Part B (n = 14): in different animals, 120 min of reperfusion was allowed, and cerebral injury (2,3,5-triphenyltetrazolium chloride stain) and edema (specific gravity) were assessed. Part C (n = 4): in different animals, the blood-brain barrier was evaluated by electron microscopy. Evans Blue (micrograms per gram brain tissue, mean +/- SD) was greater in the control (20.8 +/- 9.0) and albumin (15.5 +/- 7.3) groups versus the pentastarch (4.7 +/- 2.7) group (P less than 0.05). Brain injury (percent of hemisphere ipsilateral to occlusion) was less and specific gravity greater in the pentastarch (33 +/- 8 and 1.040 +/- 0.003 respectively) versus the albumin group (45 +/- 6 and 1.035 +/- 0.003). This study supports the hypothesis that during temporary cerebral ischemia, pentastarch decreases brain injury and edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1992

Complications of hepatic resection for colorectal carcinoma metastasis.

Hepatic resection of metastatic colorectal carcinoma is widely advocated with 5-year survival rates quoted at 20 to 25 per cent. However, concerns about the morbidity and mortality for this procedure still exist. It is estimated that only 25 per cent of patients potentially eligible for hepatic resection are actually referred for evaluation, possibly secondary to concerns about the morbidity and mortality of the surgical procedure involved. All patients undergoing such resections at the Emory University Affiliated Hospitals between January 1, 1984 and December 31, 1989 were reviewed to determine the associated morbidity and mortality. Forty-three patients were identified (23 men, 20 women, ranging in age from 32 to 80 years (mean of 60.8). The average postoperative intensive care unit (ICU) stay was 3.2 days (range 1 to 12) and the average hospital stay was 15 days (range 6 to 45). There were no postoperative deaths, and 10 patients (23%) developed significant complications (1 biliary fistula, 2 thrombophlebitis, 3 abscess/wound infections, 1 hepatic insufficiency, 1 pneumothorax, 1 pleural effusion, 1 lobar pulmonary collapse). The occurrence of complications was not related to preoperative liver enzymes, absolute tumor mass present, or associated co-morbid disease. The extent of liver resection, length of operation, and number of units of blood transfused were all correlated with the occurrence of complications (P = 0.01, 0.01, and 0.05, respectively). Likewise, the length of hospital stay and ICU stay were directly related to the extent of hepatic resection (P = 0.05 and 0.09) and number of transfusions (P = 0.05 and 0.01). The length of operation showed such a trend but was not statistically significant (P = 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Delayed institution of hypertension during focal cerebral ischemia: effect on brain edema.

The effect of induced hypertension instituted after a 2-h delay following middle cerebral artery occlusion (MCAO) on brain edema formation and histochemical injury was studied. Under isoflurane anesthesia, the MCA of 14 spontaneously hypertensive rats was occluded. In the control group (n = 7), the mean arterial pressure (MAP) was not manipulated. In the hypertensive group (n = 7), the MAP was elevated by 25-30 mm Hg beginning 2 h after MCAO. Four hours after MCAO, the rats were killed and the brains harvested. The brains were sectioned along coronal planes spanning the distribution of ischemia produced by MCAO. Specific gravity (SG) was determined in the subcortex and in two sites in the cortex (core and periphery of the ischemic territory). The extent of neuronal injury was determined by 2,3,5-triphenyltetrazolium staining. In the ischemic core, there was no difference in SG in the subcortex and cortex in the two groups. In the periphery of the ischemic territory, SG in the cortex was greater (less edema accumulation) in the hypertensive group (1.041 +/- 0.001 vs 1.039 +/- 0.001, P less than 0.05). The area of histochemical injury (as a percent of the cross-sectional area of the hemisphere) was less in the hypertensive group (33 +/- 3% vs 21 +/- 2%, P less than 0.05). The data indicate that phenylephrine-induced hypertension instituted 2 h after MCAO does not aggravate edema in the ischemic core, that it improves edema in the periphery of the ischemic territory, and that it reduces the area of histochemical neuronal dysfunction.

Animals↗
PubMed1991

Time- and pressure-dependent changes in blood-brain barrier permeability after temporary middle cerebral artery occlusion in rats.

After 180 min of temporary middle cerebral artery occlusion in rats, the affect of phenylephrine-induced hypertension on blood-brain barrier permeability was assessed. One of the following blood-pressure regimens was maintained during either a 30- or 120-min period of reperfusion: (a) 30/Norm, 30 min of normotensive reperfusion was allowed; (b) 30/HTN, mean arterial blood pressure was increased by 35 mm Hg during 30 min of reperfusion; (c) 120/Norm, 120 min of normotensive reperfusion was allowed; or (d) 120/HTN, mean arterial blood pressure was increased by 35 mm Hg during 120 min of reperfusion. Evans blue (30 mg/kg) was given, and brains were analyzed for Evans blue by spectrophotometry. Evans blue (microgram/g brain tissue, mean +/- SD) was greater (P less than 0.05) in both hypertensive groups versus their time matched normotensive groups (30/HTN: 80 +/- 16 versus 18 +/- 6 in the 30/Norm group; 120/HTN: 17 +/- 6 versus 8 +/- 3 in the 120/Norm group). In addition, Evans blue was greater (P less than 0.05) in both 30-min groups versus their pressure matched 120-min groups (30/Norm: 18 +/- 6 versus 8 +/- 3 in the 120/Norm group; 30/HTN: 80 +/- 16 versus 17 +/- 6 in the 120/HTN group). The data are consistent with previous studies which have demonstrated an opening of the blood-brain barrier at the onset of reperfusion. In addition, the data support a hypothesis that changes in blood-brain barrier permeability are more sensitive to hypertension in the early period of reperfusion.

Animals↗
PubMed1991

A comparison of the area of histochemical dysfunction after focal cerebral ischaemia during anaesthesia with isoflurane and halothane in the rat.

The investigations that have thus far evaluated the cerebral protective properties of isoflurane have provided conflicting results. Protection would be most likely to occur in the circumstances of incomplete cerebral ischaemia in which there is a penumbral zone of marginal perfusion. The present investigation sought to evaluate further the protective properties of isoflurane in that circumstance. Middle cerebral artery occlusion (MCAO) was performed in Sprague-Dawley rats anaesthetized with 1.2 MAC concentrations of either halothane or isoflurane. At the end of four hours of MCAO, the brains were removed, sectioned and incubated in the histochemical stain 2-3-triphenyltetrazolium (TTC). An image analysis system was used to measure the area of reduced or absent TTC staining in four coronal planes spanning the distribution of the middle cerebral artery. There was no difference between halothane and isoflurane anaesthetized animals with respect to the area of brain with evidence of histochemical dysfunction. It is concluded that isoflurane is not protective (relative to the status of halothane anaesthetized control animals) when administered at 1.2 MAC concentration during four hours of focal (incomplete) cerebral ischaemia in the rat.

Anesthesia, Inhalation↗
PubMed1991

Persistent sacral nerve root deficits after continuous spinal anaesthesia.

Neurological deficits following spinal anaesthesia are rare. We report two cases of persistent sacral nerve root deficits after continuous spinal anaesthesia (CSA) performed with hyperbaric lidocaine through a lumbar microcatheter. In both cases the dose of 5% lidocaine (5.7 and 4.3 ml) was greater than usual. In the immediate postoperative period the constellation of neurological deficits included perianal hypaesthesia, lower extremity paresis, urinary retention, and difficult defaecation. Both patients have residual perianal hypaesthesia and difficult defaecation. In these cases, the high-dose requirements of local anaesthetic via microcatheter CSA with focal sensory block suggests nonuniform distribution of the hyperbaric lidocaine. Microcatheter CSA may convey a unique risk of maldistribution of the local anaesthetic solution and local neurotoxicity.

Aged↗
PubMed1991

Induced hypertension during restoration of flow after temporary middle cerebral artery occlusion in the rat: effect on neuronal injury and edema.

The effect of hypertension instituted during restoration of flow after focal ischemia was studied. After the middle cerebral artery (MCA) of 12 rats was occluded for 2 hours, the ligatures were released and flow was restored for a period of 2 hours. In the control group, mean arterial pressure (MAP) was not manipulated. In the hypertensive group, the MAP was elevated by 25-30 mm Hg immediately after reestablishment of MCA patency. The area of neuronal injury, determined by 2,3,5-triphenyltetrazolium staining, was significantly smaller in the hypertensive group. Specific gravity, determined by microgravimetry, did not differ between groups. The data demonstrate that modest hypertension, when induced during reperfusion after 2 hours of MCA occlusion, reduces neuronal injury and does not exacerbate edema formation.

Analysis of Variance↗
PubMed1991

L-644,711, a novel anion transport inhibitor, increases isoflurane MAC in rats.

The effect of the anion transport inhibitor L-644,711 on isoflurane MAC was determined in rats (n = 24). After baseline MAC determination, each rat received one of the following drug protocols: (a) control, vehicle only; (b) L-644,711IT, a 3-mg/kg intrathecal bolus of L-644,711 followed by an infusion at 1.5 mg.kg-1.h-1; or (c) L-644,711IV, a 6-mg/kg intravenous bolus of L-644,711 followed by an infusion at 3 mg.kg-1.h-1. MAC was again determined. The baseline isoflurane MAC was not different between groups (control, 1.52% +/- 0.15%; L-644,711IT, 1.51% +/- 0.24%; L-644,711IV, 1.54% +/- 0.13% [mean +/- SD]). After drug or vehicle administration, isoflurane MAC was larger for the L-644,711IT group (2.25% +/- 0.17%) versus the control (1.38% +/- 0.13%) and L-644,711IV (1.39% +/- 0.15%) groups (P less than 0.05). These data are consistent with the hypothesis that isoflurane anesthesia is influenced by anion channels and that blocking these channels may reduce the pharmacodynamic potency of isoflurane.

Anesthesia, Inhalation↗