Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage

A review of pre- and postoperative prone knee flexion (PKF) data after isolated hamstring tenotomy for 52 patients with cerebral palsy (CP) at an average follow-up of 3 years 4 months showed the frequency of diminished knee flexion to be 71%. Twenty-three percent of the knees actually had improved flexion, whereas 6% were unchanged. On the average, patients' flexion decreased 14.4 degrees from a preoperative PKF of 131.5 degrees to 117.1 degrees postoperatively (p < 0.0001). Only 11.5% of patients had PKF < 90 degrees at most recent follow-up, however; only 1.9% had PKF < 60 degrees. Thirteen percent of ambulators eventually required a rectus femoris transfer to correct "stiff-legged gait."     

Intraocular concentrations of chemotherapeutic agents after systemic or local administration

OBJECTIVES: To investigate the concentrations of carboplatin and etoposide achieved in the aqueous and vitreous humors after intravenous infusion in nonhuman primates, and to investigate whether local administration of carboplatin might result in higher concentrations in the vitreous humor. METHODS: Macaca fascicularis primates were treated with 1 of 3 regimens: (1) intravenous carboplatin (18.7 mg/kg), etoposide (5 mg/kg), and vincristine sulfate (0.05 mg/kg), (2) peribulbar carboplatin (10 mg/mL), or (3) episcleral balloon carboplatin (10 mg/mL). Concentrations of chemotherapeutic agents were measured in the plasma and in the aqueous and vitreous humors. RESULTS: No measurable amount of etoposide was detected in the aqueous or vitreous humor after intravenous administration. Mean measured peak vitreous concentration of carboplatin after intravenous administration was 0.31 microg/mL, which was 1% of the peak plasma value. Mean measured peak vitreous concentrations of carboplatin after peribulbar or episcleral balloon administration were 2.38 microg/mL and 2.95 microg/mL, respectively, which represent 7.68- and 9.52-fold increases over the concentration achieved after intravenous administration. No serious toxic effect was observed in any animal. CONCLUSIONS: Peribulbar and episcleral balloon administration of carboplatin seemed to be safe and resulted in higher vitreous concentrations than intravenous administration in this model. These results suggest that these alternate routes of delivery should be explored in children with vitreous seeding of retinoblastoma.     

Intracerebral hemorrhage after carotid endarterectomy: incidence, contribution to neurologic morbidity, and predictive factors

PURPOSE: With a diminishing rate of cardiac and neurologic events after carotid endarterectomy, intracerebral hemorrhage is gaining increasing importance as a cause of perioperative morbidity and mortality. To date, information has been largely anecdotal, and there has been no comparison with a control group of patients. METHODS: The records of all patients experiencing symptomatic intracerebral hemorrhage after carotid endarterectomy were reviewed and compared with data from 50 randomly selected patients who did not experience intracranial bleeding. Univariate analyses were performed, using the Fisher exact test for dichotomous data and the Student t test for continuous data. RESULTS: During a 6-year period, symptomatic intracranial hemorrhage developed in 11 (0.75%) of 1471 patients undergoing carotid endarterectomy, accounting for 35% of the 31 total perioperative neurologic events. Hemorrhage occurred a median of 3 days postoperatively (range, 0 to 18 days). Signs and symptoms included hypertension in all 11 patients, headache in 7 conscious patients (64%), and bradycardia in 6 patients (55%). Massive hemorrhage with herniation and death occurred in 4 patients (36%). Moderate hemorrhage developed in 5 patients (45%); 3 of these patients had partial recovery, and 2 had complete recovery. Petechial hemorrhage occurred in the remaining 2 patients (18%), 1 with partial and 1 with complete recovery. In comparison with the control group, there were no differences in respect to sex, indication for operation, smoking or diabetic history, and antiplatelet therapy or perioperative heparin management. Patients with intracranial hemorrhage were, however, younger, more frequently hypertensive, had a higher degree of ipsilateral and contralateral carotid stenosis, and had a higher rate of contralateral carotid occlusion. CONCLUSION: Intracranial hemorrhage occurs with notable frequency after carotid endarterectomy and accounts for a significant proportion of neurologic morbidity and mortality. Younger patients, hypertensive patients, and patients with severe cerebrovascular occlusive disease appear to be at greatest risk for the complication.     

Rectal administration of anesthetic agents

OBJECTIVES: To collect data in the current literature dealing with the diffusion, the reliability and the effectiveness of the rectal administration of anaesthetic drugs. To evaluate differences with parenteral administration. DATA SOURCES: Pharmacokinetics and clinical studies published in recent years in indexed journals. STUDY SELECTION: Based on the study methodology, drugs employed and pharmacokinetic parameters evaluated. DATA EXTRACTION: Factors involved in absorption of drugs from the rectal mucosa, clinical effect and pharmacokinetic data of the following drugs: diazepam, flunitrazepam, midazolam, ketamin and methohexital, then a brief evaluation of other drugs: thiopental, etomidate, morphine and chloral hydrate. DATA SYNTHESIS: The most widely used drugs are benzodiazepines: they are safe, easy to manage and highly effective; among them midazolam has the best kinetic and dynamic pattern. Ketamin is useful during painful diagnostic procedures; with the use of barbiturates there is a greater risk of respiratory depression and more caution must be employed. CONCLUSIONS: Wide intervariability of rate of absorption, achievement of plasma levels and clinical effect is a relevant drawback of this technique, such to make it not preferable to the parenteral route, when both are feasible. It deserves, anyway, more consideration, and maintains its validity for the preparation of the paediatric patient to general anaesthesia.     

Intracerebral inflammation after human brain contusion

OBJECTIVE: This study was undertaken to analyze the inflammatory components in contused human brain tissue to compare the findings with previous experimental data regarding the pathogenesis of brain contusions. METHODS: Contused brain tissue biopsies were obtained from 12 consecutive patients undergoing surgery for brain contusions 3 hours to 5 days after trauma. Inflammatory and immunological components were analyzed by immunohistochemistry. RESULTS: In patients undergoing surgery less than 24 hours after trauma, the inflammatory response was limited to vascular margination of polymorphonuclear cells. In patients undergoing surgery 3 to 5 days after trauma, however, a massive inflammatory response consisting of monocytes/macrophages, reactive microglia, polymorphonuclear cells, and CD4- and CD8-positive T lymphocytes was detected. Human lymphocyte antigen-DQ was expressed on reactive microglia and infiltrating leukocytes in the late patient group. In addition, CD1a, which is a marker for antigen-presenting dendritic cells, was detected in a subgroup of microglial cells. CONCLUSION: The results corroborated hypotheses derived from experimental data. In the early phase after contusional trauma, inflammation is mainly intravascular and dominated by polymorphonuclear cells. The inflammation was parenchymal in patients undergoing surgery 3 to 5 days after trauma. The brain swelling seemed to be biphasic, the delayed phase correlating with a parenchymal inflammation. The inflammatory cells may produce several potentially harmful effects, such as acute cellular degeneration; they may also lead to degenerative long-term effects.     

An increase in renal dopamine production after the administration of radiographic contrast agents

Renal vasoconstriction and anti-natriuresis conditioned by radiographic contrast agents (CA) may be antagonised by the administration of exogenous dopamine. However, the influence of CA on the activity of renal synthesis of dopamine has not been studied. This study assessed the daily urinary excretion of dopamine, its precursor. L-3, 4-dihydroxyphenylaline (L-DOPA), and its metabolites (acid 3, 4-dihydroxyphenylacetic, DOPAC; homovanillic acid, HVA) 24 hours before and 48 hours following administration of a non ionic and hyposmolar (lopromide) CA in patients (n = 10; average age 61.3 +/- 4.3 years) submitted to coronary angiography. Urinary excretion of noradrenalin, a marker of sympathetic activity, was also assessed during the same period. The deputation of creatinine (Ccr) and the urinary excretion of sodium (UNa+) lowered after the administration of the CA (Ccr, 79.2 +/- 10.2 vs 72.2 +/- 9.6 ml/min/1.73 m2, p < 0.05; UNa+, 112.8 +/- 9.6 vs 61.7 +/- 25.1 mmol/24 h, p < 0.05). On the contrary, the urinary excretion of potassium increased in the period of 24 h following the administration of the AC (31.7 +/- 5.2 vs 103.8 +/- 10.8 mmol/24 h, p < 0.05). There was an increase in the urinary excretion of dopamine as well as noradrelalin during the 24 hour period following the administration of the CA (dopamine, 1260.2 +/- 196.8 vs 1571.5 +/- 170.2 mmol/24 h p < 0.5; noradrenalin, 186 +/- 36.6 mmol/24 h, p < 0.05). On the contrary, the urinary excretion of L-DOPA lowered after the administration of the CA (115.4 +/- 25.5 vs 80.5 +/- 13.2 mmol/24 h, p < 0.05). These results conditioned an increase in the dopamine/L-DOPA ratio in the urine, after the administration of the CA (12.2 +/- 1.5 vs 22.2 +/- 4.5 mmol/24 h, p < 0.05). In conclusion, the administration of CA is accompanied by an increase in the renal production of dopamine which, in these conditions, may act as a compensatory natriuretic hormone.     

Contact vasculitis caused by topical agents with non-steroidal anti-inflammatory agents or analgesics

INTRODUCTION: Topical non steroidal antiinflammatory drugs (NSAID) are recently used in France. Seven cases of contact vasculitis due to topical NSAID are reported. PATIENTS AND METHODS: The clinical and histological features and follow-up data of seven patients with contact vasculitis due to topical NSAID were retrospectively reviewed. RESULTS: The mean age of the seven patients (four women, three men) was 39 years. The topical NSAID used were: ketoprofene in four cases, mephenesine in one case and phenylbutazone in two cases. Cutaneous lesions occurred after a mean time of four days. Histological examination of a skin biopsy specimen showed a leucocytoclastic vasculitis in two cases, a lymphocytic vasculitis in two cases and a mixed vasculitis in three cases. Previous sensibilization to the drug was noted in five cases. Cutaneous patch tests with the drugs were positive in all cases. CONCLUSION: The risk of systemic reaction after oral ingestion of the culprit drug may be considered in these patients.     

Intracerebral hemorrhage in blacks. Risk factors, subtypes, and outcome

BACKGROUND AND PURPOSE: Blacks are at a higher risk for intracerebral hemorrhage (ICH) than whites; however, few data are available regarding the demographic and clinical characteristics of ICH among blacks. METHODS: We determined the frequency of risk factors, etiologic subtypes, and outcome among consecutive black patients admitted with nontraumatic ICH to a university-affiliated public hospital. RESULTS: The most common risk factors in the 403 black patients with ICH were preexisting hypertension (77%), alcohol use (40%), and smoking (30%). Among the 91 nonhypertensive patients, 21 (23%) were diagnosed with hypertension after onset. Compared with women, men had a younger age of onset (54 versus 60 years; P < .001) and higher frequency of alcohol use (54% versus 22%; P < .001) and smoking (39% versus 17%; P < .001). ICH secondary to hypertension (n = 311) and of undetermined etiology (n = 73) were the most common subtypes in blacks. Patients aged 65 years and older (compared with those aged 15 to 44 years; P = .001) and women (compared with men; P = .02) were more likely to be dependent at discharge. CONCLUSIONS: Primary preventive strategies are required to reduce the high frequency of modifiable risk factors predisposing to ICH in blacks.     

Intracerebral hemorrhage and treatment with platelet aggregation inhibitors: study of 21 cases

INTRODUCTION: The place of platelet antiaggregants in the aetiology of intracerebral hemorrhage (IH) has not been extensively studied. OBJECTIVE: To analyze the characteristics of IH in patients treated with platelet antiaggregants and the possible clinical and prognostic differences from other primary IH. PATIENTS AND METHODS: A retrospective study of patients admitted to hospital with primary IH from 1985 to 1997. The cases were IH patients while being treated with platelet antiaggregants. For each case we selected two controls with IH and similar age and IH risk factors. The following data was analyzed: start of clinical condition; type, dose, indication and duration of treatment with antiaggregants; mortality, localization, volume and extension of IH to the ventricles. The last four variables were compared with the control group using the ji squared test (chi 2) and the t student test. RESULTS: 21one patients had a primary IH while being treated with antiaggregants: 20 with salicylates (17 aspirin and 3 riflusal) and one with ticlopidine. The dose of aspirin was 500 mg or less in 90% of the cases. In the group treated with salicylates, this was given for more than 20 months in 90% of the cases. Initially there was no clinical progression in any case. No significant differences were observed between the variable compared, although there was a tendency to greater volume, extension to the ventricles and mortality in the group treated with antiaggregants. CONCLUSIONS: More studies with larger numbers of patients are necessary to be able to confirm the tendencies observed.     

Treatment of Herpes simplex virus infections with topical antiviral agents

Clinical studies of topical therapy against Herpes simplex virus (HSV) infections have been reviewed. Idoxuridine (IDU) 15% in dimethyl sulfoxide (DMSO), interferons, and penciclovir result in significant clinical benefit against this virus. IDU reduced pain duration and decreased time to loss of crust in a study of 301 patients. Alpha-interferon has shown synergism with other anti-HSV drugs such as caffeine, trifluorothymidine (TFT), DMSO, and nonoxynol-9. Finally, in a study of over 2,000 patients, application of penciclovir cream, both early and late in the course of HSV infection, decreased the duration of lesions, pain, and viral shedding. Acyclovir (ACV)-resistant strains of HSV are susceptible to (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and ascorbic acid shows promising effects against HSV. Using a vehicle that enhances skin penetration of a drug or possibly further exploring combination therapy may result in efficacious treatment of HSV. The possibility of topical vaccination or topical gene therapy may also prove beneficial in the future.     

Permeability characteristics of novel mydriatic agents using an in vitro cell culture model that utilizes SIRC rabbit corneal cells

The purpose of this study was to evaluate the permeability characteristics of a previously reported in vitro corneal model that utilizes SIRC rabbbit corneal cells and to investigate the permeability of three novel esters of phenylephrone chemical delivery systems (CDS) under different pH conditions using this in vitro model. The SIRC rabbit corneal cell line was grown on transwell polycarbonate membranes, and the barrier properties were assessed by measuring transepithelial electrical resistance (TEER) using a voltohmmeter. The permeabilities of esters of phenylephrone CDS across the SIRC cell layers were measured over a pH range 4.0-7. 4. The esters tested include phenylacetyl (1), isovaleryl (2), and pivalyl (3). The SIRC rabbit corneal cell line, when grown on permeable filters, formed tight monolayers of high electrical resistance with TEER values increasing from 71.6 +/- 20.8 Omega.cm2 at day 3 in culture to 2233.42 +/- 15.2 Omega.cm2 at day 8 in culture and remained constant through day 14 in culture. The transepithelial permeability coefficients (Papp) at pH 7.4 ranged from 0.58 x 10(-6) cm/s for the hydrophilic marker, mannitol, to 43. 5 x 10(-6) cm/s for the most lipophilic molecule, testosterone. The Papp at pH 7.4 for phenylephrine was 4.21 x 10(-6) cm/s. The Papp values and the lag times of the three esters of phenylephrone were pH dependent. The Papp for 1, 2, and 3 at pH 7.4 were 14.76 x 10(-6), 13.19 x 10(-6), and 12.86 x 10(-6) cm/s, respectively and the permeabilities decreased at conditions below pH 7.4. The lag times at pH 7.4 were 0.10, 0.17, and 0.12 h for 1, 2, and 3, respectively, and the values increased at lower pH conditions. The TEER values of SIRC cell line observed at day 8 to day 14 in the present investigation are similar to the resistance value reported for rabbit cornea (2 kOmega.cm2). All the esters showed significantly (p < 0.05) higher permeabilities than phenylephrine at pH 7.4. The rate and extent of transport of the drugs across the cell layers were influenced by the fraction of ionized and un-ionized species and the intrinsic partition coefficient of the drug. The results indicate that the permeability of ophthalmic drugs through ocular membranes may be predicted by measuring the permeability through the new in vitro cell culture model.     

Repeated topical administration of fenoterol in rabbit reverses its initial ocular hypotensive effect and decreases sensitivity of adenylyl cyclase in ciliary processes to stimulatory agents

PURPOSE: The effects of repeated topical administration of the selective beta 2-adrenergic agonist fenoterol on the intraocular pressure and on the adenylyl cyclase activity in ciliary processes in rabbit were examined in order to detect their possible causal relationship. METHODS: Intraocular pressure was measured by pneumatonometry. Adenylyl cyclase activity in homogenates of ciliary processes was assayed ex vivo by measurement of conversion of 32P-alpha-ATP to 32P-cyclic AMP. RESULTS: A single topical dose of 1% solution of fenoterol elicited a clear-cut decrease of the intraocular pressure lasting for several h. Repeated administration of fenoterol for 2-5 days led to a significant increase of intraocular pressure, observable from the second to the fifth day. The stimulation of adenylyl cyclase activity ex vivo by isoproterenol, vasoactive intestinal polypeptide or forskolin was significantly decreased on the fifth day (24 h after the administration of the last dose of fenoterol). CONCLUSIONS: Our data showed that repeated topical administration of the selective beta 2-adrenergic agonist increased intraocular pressure and desensitized adenylyl cyclase in ciliary processes; if these two effects are related then they would support the idea of direct relationship of decreased cAMP production in ciliary processes to the increase of intraocular pressure, and vice versa. However, conclusive evidence of this suggestion and of its possible significance in another animal species or man would require further study.     

Control of Candida albicans murine vaginitis by topical administration of polycarbophil-econazole complex

The complexation of econazole with the mucoadhesive polycarbophil was found to significantly improve the therapeutic benefit of the drug in the topical treatment of experimental vaginal candidiasis in mice, while no difference in the antimycotic activity exerted by econazole and polycarbophil-econazole could be detected in vitro.     

Prevention of thrombosis in arterial and venous microanastomoses by using topical agents

A replantation model, using the rat's foot severed at the ankle and replanted on an extended vascular pedicle, was used to study the effect of topical vasodilators in preventing microvascular thrombosis. Magnesium sulfate, Xylocaine, and papaverine gave arterial patency rates of 89% or more, compared to 65% for saline alone. There was no appreciable effect on the venous patency rates. The possible mechanisms of action for the various drugs are discussed.