Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year experience

BACKGROUND AND PURPOSE: Despite the widespread use of angioplasty, adjunct chemical therapy is often needed to treat patients with cerebral vasospasm. In this study, we examined the safety of intraarterial administration of verapamil to patients with cerebral vasospasm. We herein summarize our 2-year experience with this treatment. METHODS: We retrospectively reviewed the procedure reports, anesthesia records, clinical charts, and brain images of 29 patients who received intraarterially administered verapamil in 34 procedures for the treatment of vasospasm after subarachnoid hemorrhage from July 1998 to June 2000. The average changes in mean arterial pressure and heart rate were used to measure cardiovascular side effects. The neurologic effects were assessed by angiographic findings, the results of neurologic examinations performed before and after the procedure, and findings of CT of the head. RESULTS: The average dose of verapamil per patient was 3 +/- 0 mg or 44 +/- 5 mcg/kg. The average changes in mean arterial pressure at 10 and 20 minutes were -5 +/- 1 mm Hg and -2 +/- 1 mm Hg or -3.8 +/- 1.0% and -1.7 +/- 1.1%, respectively. No significant change of heart rate was observed at 10 minutes. The patients showed no sign of increased intracranial pressure by hemodynamic parameters, neurologic examination, or CT of the head. On 10 occasions, when the effect of verapamil infusion was assessed angiographically, there was 44 +/- 9% increase of vessel diameter in the spastic segment. Neurologic improvement was noted after five of 17 procedures when verapamil was used as the sole treatment. CONCLUSION: Low dose verapamil is safe when administered intraarterially to patients with cerebral vasospasm. Beneficial effects are achieved in some patients, prompting further study of its efficacy.     

Activation of p44/42 mitogen activated protein kinases in thrombin-induced brain tolerance

BACKGROUND: Our recent studies have shown that prior intracerebral injection of a low dose of thrombin attenuates the brain edema formation that results from either an intracerebral hematoma, an intracerebral injection of a large dose of thrombin or cerebral ischemia. The aim of the current study is to investigate whether thrombin-induced tolerance (thrombin preconditioning; TPC) is associated with activation of p44/42 mitogen activated protein (MAP) kinases. METHODS: This study contained three parts. In the first, rats received an intracerebral infusion of either saline or one unit thrombin (the TPC dose) into the right caudate nucleus. After 1, 3 and 7 days, the rats will be killed and brains used to detect p44/42 MAP kinases activation using Western blot analysis and immunohistochemistry. In the second and third parts, rats received intracerebral infusions of either vehicle, one unit thrombin (TPC) or one unit thrombin and 5 nmol PD 098059. These rats were either killed to detect kinases activation after 24 h or received a second intracerebral infusion of five-unit thrombin 7 days later with brain edema being assessed after a further 24 h. RESULTS: Western blot analysis demonstrated that p44/42 MAP kinases were activated in the ipsilateral basal ganglia after the intracerebral infusion of thrombin one unit. Cells immunoreactive for activated p44/42 MAP kinases were found in the ipsilateral basal ganglia and ipsilateral cortex. PD 098059, a MAP kinase kinase inhibitor, abolished thrombin-induced activation of p44/42 MAP kinases. TPC suppressed thrombin-induced brain edema while PD 098059 blocked this protective effect. The water contents in the ipsilateral basal ganglia 24 h after infusion of thrombin five units were 82.6+/-0.8%, 79.2+/-0.4% and 81.8+/-1.9% in the control, TPC alone and TPC plus PD 098059 groups, respectively. CONCLUSION: Thrombin can activate p44/42 MAP kinases within the brain and the protective effects of thrombin preconditioning on brain edema formation are related to this activation.     

Chloramphenicol-resistant Salmonella typhi in Saigon.

Chloramphenicol-resistant Salmonella typhi was detected in Saigon in September 1971. Subsequently, 163 strains of S typhi were isolated, 46 percent of which were resistant to choramphenicol by the agar-disk method. Sixty-two strains were studied by the broth-dilution method; 37 percent had minimal inhibitory concentrations for chloramphenicol greater than 250mug/ml, but all strains were susceptible to 0.4mug/ml of ampicillin and to a disk of a combination of trimethoprim and sulfamethoxazole (Bactrim). Persons infected with chloramphenicol-resistant strains of S typhi responded poorly to chloramphenicol alone, but ampicillin or the combination drug was effective.     

Arterialization of deep dorsal vein of penis for penile ischemia

Penile ischemia, a rare complication of diabetic end-stage renal disease, is usually treated by penectomy once conservative measures fail. We present a patient with diabetes mellitus and end-stage renal disease with penile ischemia that was successfully treated with an arteriovenous interposition bypass graft between the common femoral artery and the deep dorsal vein of the penis. Retrograde flow into the corpus spongiosum resulted in immediate pain relief and healing of the ischemic lesions.     

Elimination of dengue by community programs using Mesocyclops(Copepoda) against Aedes aegypti in central Vietnam

From September 2000 to June 2003, a community-based program for dengue control using local predacious copepods of the genus Mesocyclops was conducted in three rural communes in the central Vietnam provinces of Quang Nam, Quang Ngai, and Khanh Hoa. Post-project, three subsequent entomologic surveys were conducted until March 2004. The number of households and residents in the communes were 5,913 and 27,167, respectively, and dengue notification rates for these communes from 1996 were as high as 2,418.5 per 100,000 persons. Following knowledge, attitude, and practice evaluations, surveys of water storage containers indicated that Mesocyclops spp. already occurred in 3-17% and that large tanks up to 2,000 liters, 130-300-liter jars, wells, and some 220-liter metal drums were the most productive habitats for Aedes aegypti. With technical support, the programs were driven by communal management committees, health collaborators, schoolteachers, and pupils. From quantitative estimates of the standing crop of third and fourth instars from 100 households, Ae. aegypti were reduced by approximately 90% by year 1, 92.3-98.6% by year 2, and Ae. aegypti immature forms had been eliminated from two of three communes by June 2003. Similarly, from resting adult collections from 100 households, densities were reduced to 0-1 per commune. By March 2004, two communes with no larvae had small numbers but the third was negative; one adult was collected in each of two communes while one became negative. Absolute estimates of third and fourth instars at the three intervention communes and one left untreated had significant correlations (P = 0.009-< 0.001) with numbers of adults aspirated from inside houses on each of 15 survey periods. By year 1, the incidence of dengue disease in the treated communes was reduced by 76.7% compared with non-intervention communes within the same districts, and no dengue was evident in 2002 and 2003, compared with 112.8 and 14.4 cases per 100,000 at district level. Since we had similar success in northern Vietnam from 1998 to 2000, this study demonstrates that this control model is broadly acceptable and achievable at community level but vigilance is required post-project to prevent reinfestation.     

Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT.     

Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children

An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (Na(R)). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7-5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82-102) vs 101 (93-110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2-8.1) vs 8.0 (7.6-8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an Na(R) isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever.     

Intravenous immunoglobulin in neurological disorders: a mechanistic perspective

Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over 25 years. It is a safe preparation with no long-term side effects. IVIg was first demonstrated to be effective in autoimmune disorders, two decades ago, in the treatment of acute immune thrombocytopenia. Since then, the therapeutic efficacy of IVIg has been established in Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), myasthenia gravis (MG), dermatomyositis (DM), Kawasaki syndrome and the prevention of graft-versus-host disease in recipients of allogeneic bone marrow transplants and reported in a large number of other autoimmune and systemic inflammatory conditions.