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Biomedical subjects

M Grace

Publications and source records attributed to M Grace.

At least 199 records · Page 11Linked to original sources
PubMed1989

Trends in blood pressure, osmolality and electrolytes after subarachnoid hemorrhage from aneurysms.

Daily trends in blood pressure, osmolality and electrolytes were analyzed in a series of 173 operated aneurysm cases who had subarachnoid hemorrhage (SAH) and were admitted within 4 days of the ictus. High blood pressure was associated with a greater risk of mortality and the development of clinically significant vasospasm (VSP). High osmolality shortly after admission was related to mortality but not VSP. Changes in sodium and potassium had no obvious relationship to mortality or VSP.

Adolescent↗
PubMed1989

Daily trends in white blood cell count and temperature after subarachnoid hemorrhage from aneurysm.

A retrospective analysis of the cases of 173 patients operated on for aneurysms and admitted to a neurosurgical service early after subarachnoid hemorrhage was conducted with respect to white blood cell (WBC) count and highest daily temperature. Daily trends for the development of clinically significant vasospasm (VSP) as well as mortality during the hospitalization were analyzed. An admission WBC count greater than 15 x 10(9)/l was associated with 55% mortality as opposed to 25% mortality for those with a lower WBC count. The mortality of those with a temperature greater than 37.5 degrees C on Day 0 was 60%, compared with 35% for those with a lower temperature. A WBC count greater than 15 x 10(9)/l on Day 0 was associated with a VSP rate of 40%; a lower WBC count was associated with a VSP rate of 30% Day 0 temperatures greater than 37.5 degrees C were associated with a VSP rate of 40%, while patients with lower temperature had a VSP rate of 30%. By Day 6, the patients with temperatures greater than 37.5 degrees C had a VSP rate of 60%, double that of the VSP rate of those with temperatures less than 37.5 degrees C. WBC count was apparently more closely linked to the chance of dying than the chance of developing VSP. The development of fever after a few days is related to both increased mortality and increased chance of developing VSP.

Adolescent↗
PubMed1989

Prospective trial of timing of bacillus Calmette-Guérin vaccination in Canadian Cree infants.

We studied 184 Cree Indian infants in randomized, prospective fashion to assess the effect of age on lymphocyte sensitization to purified protein derivative (PPD) before and after and without bacillus Calmette-Guérin (BCG) vaccination. Lymphocyte responses to PPD, Candida, and streptokinase were measured at birth and at intervals later. The mean response of paired values from 26 infants without BCG vaccination rose for the PPD stimulation index (SI) from 2.7 at birth to 3.9 before 2 yr of age. The SI for both Candida and streptokinase for this group of infants rose significantly in the first 2 yr (p less than 0.05). In 66 infants who received BCG in the first 7 days of life, the PPD-SI rose from 3.1 to 35.3 (p less than 0.001). In 17 infants who received the vaccine later but before 9 months, it rose from 3.1 at birth to 24.9, and in 14 who received it between 9 months and 2 yr, it rose from 2.2 to 52.9. The lymphocyte responses to PPD after BCG in these two groups were significantly different (p less than 0.05). There was no evidence in the older infants that a raised PPD-SI before BCG vaccination affected lymphocyte sensitization by the vaccine. We conclude that increasing the age at vaccination with BCG from birth to more than 9 months enhances immunologic sensitization to PPD significantly in this population.

Adult↗
PubMed1989

A trial of the 21-aminosteroid U74006F in a primate model of chronic cerebral vasospasm.

The efficacy of U74006F in the prophylaxis of chronic cerebral vasospasm (VSP) was evaluated in a randomized, double-blind, placebo-controlled trial. Forty cynomolgus monkeys were divided by restricted randomization into 2 treatment groups of 20. Five animals from each treatment group were randomized into subgroups 1 and 2. The animals of subgroup 1 were studied pathologically. Brain biopsies of the animals in subgroup 2 were performed and studied with high-performance liquid chromatography (HPLC). The remaining 20 animals supplemented the number studied angiographically. Significant VSP (P less than 0.05) was detected in the majority of vessels from the clot site (right) of both treatment groups. Electron microscopy results showed positive correlation with the angiographic data. When comparing the effects of U74006F to those of the placebo at day 7, there was a significant difference (P less than 0.05) in the degree of VSP in the right extradural internal carotid and right middle cerebral arteries. This resulted from a greater degree of VSP in placebo animals. Two animals developed delayed ischemic deficits, one from each group. The infarct of the U74006F animal was smaller than the infarct in the placebo animal. Although overall changes in phosphagen levels did not reach statistical significance, HPLC analysis of the cortical biopsies did show a decrease in the ATP/ADP +/- AMP ratio of 54% in placebo animals and only 7% in animals receiving U74006F. The middle cerebral arteries of 2 animals were also studied with HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Safety and efficacy of intrathecal thrombolytic therapy in a primate model of cerebral vasospasm.

To test the safety of a large intrathecal dose of human recombinant tissue plasminogen activator (rt-PA), 6 cynomolgous monkeys were given 10 mg of rt-PA (mean, 2.7 mg/kg) through an Ommaya reservoir after craniectomy and dissection of the basal cisterns. Bleeding occurred briefly at the incision in 2 animals; otherwise the clinical condition of all 6 remained normal throughout the postoperative period. Systemic fibrinolysis did not occur, and gross and microscopic examination of the brain and meninges revealed no abnormality. Next, we evaluated the efficacy of unilateral administration of rt-PA suspension (0.5 mg) plus slow-release gel rt-PA (1.25 mg) in lysing a bilateral subarachnoid clot and preventing vasospasm in a randomized, placebo-controlled trial. Sixteen monkeys were divided randomly into 2 equal groups, each of which underwent baseline cerebral angiography, followed by frontotemporal craniectomy and induction of subarachnoid hemorrhage on the left side and then on the right. Before closure on the right side either rt-PA or an equal volume of placebo was injected into the subarachnoid space. On day 7 angiography was repeated, and the animals were killed under anesthesia for necropsy. One of the animals in the placebo group developed a cerebral infarction on day 5. In the placebo group significant vasospasm occurred in all major right and left-sided anterior cerebral vessels (P less than 0.01). No vasospasm occurred in the rt-PA-treated animals. Whereas gross subarachnoid clot was found in all animals in the placebo group (mean clot weight 1.13 g), only a small fragment of clot was found in a single rt-PA-treated animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Herpes labialis treatment with acyclovir 5 per cent ointment.

Eighty patients who were culture-confirmed positive for recurrent herpes labialis were entered into a clinical trial. Sixty of these completed two episodes each in a randomized, double-blind, placebo-controlled clinical trial of 5 per cent acyclovir in a polyethylene glycol ointment base. The 5 per cent acyclovir ointment failed to show better clinical healing effects than placebo in both documented episodes. There were no serious side effects observed in either group.

Acyclovir↗
PubMed1988

Treatment of herpes labialis with acyclovir. Review of three clinical trials.

Three trials with acyclovir in the treatment of recurrent herpes labialis in the same patient population are reviewed. In the first trial, oral acyclovir capsules, five times per day for five days, were shown to be of significant benefit for some parameters of cutaneous resolution in three successive episodes. Topical formulations were evaluated in two separate trials; 5 percent acyclovir in a modified aqueous cream base exhibited favorable trends, but 5 percent acyclovir in a polyethylene base was ineffective. A high dose of oral acyclovir may offer the most effective method of control of recurrent herpes labialis.

Acyclovir↗
PubMed1988

Effect of morphine and nalmefene on energy balance in diabetic and non-diabetic rats.

Male rats made diabetic by intravenous injection of streptozotocin were used to evaluate the effect of the diabetic state on morphine- and nalmefene-induced changes in food intake and body weight. Morphine increased 4 hour food intake in non-diabetic rats after an initial injection, but increased intake in diabetic rats only after repeated injections. Unlike short term measurements, morphine decreased food intake when measured over 24 or more hours in both groups. Chronic injection of morphine decreased body weight only in non-diabetic rats. Feed efficiency data suggest that morphine had a more potent effect on energy balance in the non-diabetic rats. The opioid antagonist, nalmefene, did not alter body weight in either group and only altered food intake in the diabetic animals. These data are in concert with other reports indicating that the diabetic state renders animals less responsive to the effects of morphine on nociception and smooth muscle contraction.

Animals↗
PubMed1988

A randomized double-blind comparison of diltiazem and nifedipine in stable angina.

A double-blind crossover trial comparing diltiazem (360 mg/day) and nifedipine (120 mg/day) for treatment of stable angina was conducted in 21 of 27 patients with proven coronary artery disease who completed the trial. All patients started with a 2 week placebo period followed by a random assignment to either drug treatment for 3 weeks and subsequent crossover to the other treatment. The two drug treatment periods were separated by a 1 week placebo washout phase and the study was completed with a 1 week placebo phase. There were no significant differences between patients' responses to diltiazem and nifedipine in relation to time to onset of angina, ST depression responses to exercise, heart rate or systolic or diastolic blood pressure. A total of 37 adverse effects were reported with nifedipine compared with 9 with diltiazem in the 22 patients in whom drug safety was analyzed. Additionally, two patients treated with nifedipine were withdrawn from study participation before crossover. There was a significant (p less than 0.05) difference with respect to incidence of edema (7 of 22 patients taking nifedipine, 1 of 22 taking diltiazem) and dizziness (7 of 22 patients taking nifedipine, 0 of 22 taking diltiazem). The most frequent adverse effect reported with diltiazem was rash (3 of 22 patients). Severe adverse effects were reported in four patients: in one with diltiazem (rash) and in three with nifedipine (palpitation in two and headache in one). A reduction in prescribed dosage was required in 37% of nifedipine-treated compared with 6% of diltiazem-treated patients. Efficacy measures were significantly improved above placebo levels by both diltiazem and nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1988

Human acid beta-glucosidase: inhibition studies using glucose analogues and pH variation to characterize the normal and Gaucher disease glycon binding sites.

Comparative kinetic studies with glycon inhibitors were used to investigate the properties of the active site of human acid beta-glucosidase (EC 3.2.1.45) from normal placenta and spleens of type 1 Ashkenazi Jewish Gaucher disease (AJGD) patients. With the pure normal enzyme, the specificity of glycon binding was assessed with 35 glucose derivatives and epimers. Most glycons were mixed type inhibitors with a predominantly competitive nature (i.e., Kis much less than Kii) and had low apparent affinity for the enzyme (Kisapp = 20-500 mmol/l). beta-Glucose-1-phosphate was unusual, since it inhibited 4-methylumbelliferyl-beta-glucoside hydrolysis in an uncompetitive pattern (Kiapp = 0.55 mmol/l) but had no effect on glucosyl ceramide hydrolysis. C-1- (1-deoxy-1-amino-beta-D-glucose) and C-3- (3-deoxy-3-amino-D-glucose) amino and C-5-imino [1-deoxynojirimycin (dNM), nojirimycin and castanospermine] substituted sugars were highly potent inhibitors with Kisapp(beta-glucose)/Kisapp approximately equal to 10(3)-10(5); an amine at C-2 did not alter Kisapp compared to beta-glucose. The variation of Kisapp with pH for the 5-imino- and 1-deoxy-1-aminoglycosides conformed to a model for the unprotonated inhibitors binding to the protonated forms (EH and EH2) of the diprotic (Vmaxapp and Vmaxapp/Kmapp) normal enzyme (pK1 = 4.7; pK2 = 6.7) with pH-independent Kisapp values of 2.9-9.0 mumol/l and 0.22 mmol/l, respectively. Several of the amine-containing inhibitors competitively protected the enzyme from inactivation by conduritol B epoxide, a covalent active site-directed inhibitor, indicating interaction with residues at that site. With the partially purified AJGD splenic enzymes, the results were the same except that Kisapp(AJGD)/Kisapp(normal) = 4-17 for dNM and 1-deoxy-1-amino-beta-glucose; this ratio was approximately equal to 1 with most other glycons, and particularly, nojirimycin and castanospermine. The results of these studies indicated that the glycon binding site of the normal acid beta-glucosidase contains important residues for interaction with the C-2, C-3 and C-4 hydroxyl groups of beta-glucose and a residue with pKa = 6.7 which was critical to the binding of amine-containing inhibitors and the hydrolysis of substrates. The findings were consistent with a specific alteration in or near the glycon binding site which results in the functional abnormalities of the mutant AJGD acid beta-glucosidase.

Adult↗
PubMed1988

Effects of vasospasm on levels of prostacyclin and thromboxane A2 in cerebral arteries of the monkey.

To determine whether cerebral arteries in spasm have an altered capacity to synthesize the vasoactive substances prostacyclin and thromboxane A2, we measured levels of these arachidonic acid metabolites using a primate model of vasospasm. Twenty-four cynomolgus monkeys were assigned at random to one of three groups designated sham, clot, or clot-removal. All animals underwent base line cerebral angiography and bilateral dissection of the major cerebral arteries from the arachnoid. The clot and clot-removal groups had autologous hematomas placed around the vessels to simulate subarachnoid hemorrhages. The sham group had a similar volume of saline instilled into the subarachnoid space. Twenty-four hours later, the clot-removal group underwent a second craniotomy to remove the hematomas. Seven days after the initial operation, angiography was repeated on all animals. The animals were then killed, and the cerebral arteries were removed. Basal levels of prostacyclin and thromboxane in the cerebral vessels were measured after incubation in vitro by radioimmunoassay. No detectable leukotriene C4 release by these arteries was measurable using radioimmunoassay. Angiography revealed severe cerebral vasospasm in the clot group, but not in the clot-removal or sham groups. There were no statistical differences among the groups in thromboxane release, but prostacyclin levels were significantly lower in the clot group than in the clot-removal group (P less than 0.05). It thus seems that, if an imbalance in constrictor and dilator eicosanoids occurs in association with vasospasm, this is more likely to arise from a relative lack of the vasodilator component prostacyclin than from a surplus of the vasoconstrictor thromboxane.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Factors influencing the outcome of aneurysm rupture in poor grade patients: a prospective series.

When is the outlook hopeless after rupture of an intracranial aneurysm? Some data bearing on the answer to this important question were obtained in a prospective, multicenter trial of 184 poor grade patients in a study of the calcium antagonist nimodipine. Entry was within 3 days of subarachnoid hemorrhage (SAH). The admission work-up included angiography of the anterior and posterior circulations and computed tomographic (CT) scans. The angiograms were repeated as close to Day 8 post-SAH as possible, and the CT scans were repeated at 3 months at the time of follow-up neurological assessment. Radiological assessment was performed independently of knowledge of drug treatment or patient outcome. A discriminant function analysis indicated that the relative importance of factors prognostic for outcome was, in order of importance: whether the patient was treated surgically, neurological grade on admission, age, initial systolic blood pressure, and aneurysm size. The discriminant function analysis correctly classified 80% of our cases. A constellation of poor prognostic features will aid the neurosurgeon in treating a patient conservatively and appropriately advising relatives. The ultimate decision on how to treat a given patient continues to depend partly on clinical judgement, which remains intuitive and subject to influences not studied here.

Adolescent↗
PubMed1988

Effect of routine administration of analgesia on energy expenditure in critically ill patients.

Measurement of gas exchange using portable metabolic carts to indirectly determine energy expenditure (EE) has been a recent advance in the nutritional management of mechanically ventilated, critically ill patients. Although administration of large doses of morphine has been shown to significantly decrease EE, the influence on EE of morphine given in routine amounts to critically ill patients has not been studied previously. We examined the effect of morphine administration (given as bolus IV injections of 0.10 mg/kg every two hours and continuous IV infusion at 0.05 mg/kg/hr) on EE during rest and various ICU activities in seven mechanically ventilated patients. Morphine administration resulted in a significant reduction in resting EE and total EE of 6.0 and 8.6 percent, respectively. However, EE associated with activities (ie, chest x-ray examination and chest physiotherapy) were not significantly affected by morphine administration. Both bolus and continuous IV morphine infusion had similar effects on EE. Administration of routine doses of morphine significantly decreases total EE in critically ill patients. This should be considered an important factor influencing measurements of EE.

Calorimetry, Indirect↗
PubMed1988

Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial.

A multicenter, randomized placebo-controlled double-blind trial of nimodipine in poor-grade aneurysm patients was carried out in 17 Canadian hospitals. Of 188 patients enrolled in the trial, 32 were excluded for protocol violations and two were excluded due to statistical considerations, leaving 154 patients for valid outcome analysis. Nimodipine treatment was associated with a significantly better outcome (p less than 0.001): 21 (29.2%) of 72 nimodipine-treated patients had a good outcome at 3 months after subarachnoid hemorrhage (SAH) compared to eight (9.8%) of 82 placebo-treated patients. Delayed ischemic deficits from vasospasm alone were significantly less frequent in the nimodipine group (p less than 0.05) with permanent deficits occurring in five nimodipine-treated patients (6.9%) and in 22 placebo-treated patients (26.8%). Improvement in the good outcome rate and reduction in delayed ischemic deficits from vasospasm alone occurred in both Grade 3 and 4 patients, with no difference between nimodipine- and placebo-treated patients being found in Grade 5 patients. Repeat angiography after Day 4 was carried out in 124 patients. There was no significant difference in the incidence of moderate or severe diffuse spasm, which was seen in 64.3% of nimodipine-treated patients and 66.2% of placebo-treated patients. The authors conclude that nimodipine treatment in poor-grade patients with SAH results in an increase in the number of good outcomes and a reduction in the incidence of delayed neurological deterioration due to vasospasm. This effect occurs by a mechanism other than prevention of large-vessel spasm as visualized on angiography.

Adolescent↗
PubMed1988

Effect of intrathecal thrombolytic therapy on subarachnoid clot and chronic vasospasm in a primate model of SAH.

The safety and efficacy of the thrombolytic agent tissue-type plasminogen activator (tPA) in the elimination of subarachnoid clot and prevention of chronic vasospasm were evaluated in a blind randomized placebo-controlled trial. Twenty-four monkeys were randomly assigned to one of two groups of 12. Each group underwent baseline cerebral angiography and coagulation analysis followed by right-sided craniectomy and experimental subarachnoid hemorrhage (SAH). An Ommaya reservoir was inserted with its catheter placed into the subarachnoid space. Twenty-four hours later one group (the tPA group) received 0.5 mg of tPA in 0.5 ml of buffer injected into the reservoir every 8 hours for three doses, while the second group (the placebo group) received the same volume of normal saline. On Day 7, angiography was repeated and the animals were sacrificed. One animal from the placebo group developed a delayed ischemic neurological deficit on Day 5 after SAH. Moderate to severe vasospasm (greater than 30% reduction in vessel caliber) was present on Day 7 in the internal carotid and middle cerebral arteries of the animals in the placebo group (p less than 0.01), while in the tPA group only mild narrowing of the anterior cerebral artery was seen. No significant change in coagulation status occurred in either group. All animals in the placebo group had a large amount of subarachnoid clot remaining at the time of sacrifice, but 11 of the 12 animals in the tPA group were completely free of clot. The results of electron microscopic studies of the cerebral arteries correlated with angiography, and there was no histological evidence of brain inflammation associated with the intrathecal use of tPA.

Animals↗
PubMed1988

Randomized double blind trial comparing sotalol and propranolol in chronic ventricular arrhythmia.

Sotalol is a beta-blocker which also prolongs repolarization. Its relative efficacy towards suppressing chronic ventricular arrhythmia was tested by comparison with propranolol. This double blind parallel comparison study involved 30 patients with or without coronary artery disease who had chronic symptomatic ventricular arrhythmia and more than an average of 30 premature ventricular complexes (PVCs) per hour. After the placebo baseline period patients received four weeks of active treatment with sotalol or propranolol. Responders were patients who had 75% or more reduction of PVCs during 24 h Holter monitoring. One patient in each treatment group had intolerable side effects on a low dose of the drug and were withdrawn. Side effects were present more frequently in the propranolol group compared with sotalol. Proarrhythmic effects were present in one patient on sotalol. There was no significant difference in suppression of ventricular extrasystoles (sotalol 65%, propranolol 44%), with reduction in ventricular couplets being 99% for sotalol and 49% for propranolol. There was a significant increase in QTc in patients on sotalol. Therefore, sotalol is a well tolerated drug and may be preferable to propranolol for control of chronic ventricular arrhythmia.

Adolescent↗