Are there potential problems with generic substitution of antiepileptic drugs?: A review of issues

In response to increasing cost pressures, healthcare systems are encouraging the use of generic medicines. This review explores potential problems with generic substitution of antiepileptic drugs (AEDs). A broad search strategy identified approximately 70 relevant articles. Potential problems with generic substitution included: The limited evidence (mainly case reports with some pharmacokinetic studies) appears to support these concerns for older AEDs. As a result, restrictions on use of specific generic AEDs are in place in some countries and recommended by some lay epilepsy organisations. As more AEDs lose patent protection, it is important to examine the question of whether generic substitution may pose problems for patients with epilepsy, and whether there should be safeguards to ensure that both physician and patient are informed when generic substitution occurs.     

SUICIDE ATTEMPT DUE TO METOCLOPRAMIDE-INDUCED AKATHISIA

Akathisia as a side-effect of metoclopramide has received increasing attention in consultation-liaison psychiatry in recent years. A case of metoclopramide-induced akathisia resulting in a suicide attempt is reported in order to highlight the suffering of such patients and the factors that lead to misdiagnosis.     

An evaluation of Gambusia affinis and Bacillus thuringiensis var. israelensis as mosquito control agents in California wild rice fields

The mosquito control potential of the mosquitofish and Bacillus thuringiensis var. israelensis (Bti) were evaluated in experimental wild rice fields in Lake County, California. Fields were assigned one of six treatment: control, 1.1 kg/ha G. affinis, 3.4 kg/ha G. affinis, Bti only (6 kg/ha Vectobac granules), 1.1 kg/ha G. affinis plus Bti and 3.4 kg/ha G. affinis plus Bti. Gambusia affinis, at both release rates, significantly reduced the mosquito population at densities exceeding 100 fish/minnow trap. Treatments with Bti significantly reduced larval population; however, the populations in the fields without fish rebounded to pretreatment levels within two weeks. In fields stocked with G. affinis and treated with Bti, populations remained low after Bti treatment. Nontarget populations of arthropods were significantly lower in fields stocked with G. affinis than in fields without fish on one or more sampling dates.     

Distribution of normal and abnormal fluid collections in the glenohumeral joint: Implications for MR arthrography

Although magnetic resonance (MR) images of the glenohumeral joint frequently demonstrate intraarticular fluid, no specific criteria have, to the authors' knowledge, been published that allow accurate assessment of the amount of fluid present. Also, despite the increasing use of MR arthrography of the shoulder, the optimal amount of intra-articular fluid that should be used with this technique has not been determined. The authors progressively distended the glenohumeral joint in six cadaveric shoulder specimens with a dilute gadopentetate dimeglumine solution and obtained MR images after injection of 2, 5, 10, 15, and 20 mL of the solution. The pattern of fluid distribution was evaluated, and these results were then used to estimate the amount of fluid that was present in the glenohumeral joint on MR images of 20 shoulders obtained in 12 asymptomatic volunteers. In 14 of these shoulders, intraarticular fluid was present; however, in none was more than 2 mL evident. Results of the cadaveric study also indicated that 15 mL of intraarticular fluid appears to be the optimal amount for MR arthrography.     

Radiologische und histologische Beobachtungen an zentralen Talusfrakturen

In einer prospektiven Studie zentraler Talusfrakturen wurden radiologische Daten (Nativr?ntgenbild, CT, MRT) auf ihre Korrelation zum histologischen Befund (Biopsie zum Zeitpunkt der Schraubenentfernung) überprüft. Bei 9 Frakturen an 8 Patienten (Alter 14 – 48 Jahre) handelte es sich um Frakturen des Typs Hawkins I und II je einmal sowie des Typs III viermal; in 3 weiteren F?llen lagen K?rperfrakturen vor. Innerhalb von 24 h nach dem Unfall wurden 7 Frakturen verschraubt und 2 mit Bohrdr?hten adaptiert. Das verletzte Bein wurde für 14 – 53 Wochen post trauma vollst?ndig entlastet. Die Beobachtungszeit betrug mit einer Ausnahme 2 Jahre oder mehr; 4 Patienten zeigten am letzten R?ntgenbild einen intakten Talus, 4 Patienten zeigten partielle Einbrüche des Talusdoms und in 1 Fall war ein Teileinbruch fraglich. Die histologische Untersuchung (16 – 52 Wochen post trauma) zeigte in allen F?llen osteozytenfreien origin?ren Knochen mit Anlagerung neuen Knochens in individuell recht unterschiedlichem Ausma?. Das Hawkins-Zeichen war in 6 F?llen partiell positiv, sowie je einmal positiv und einmal negativ. Im CT konnte sowohl Dekalzifikation als auch Frakturheilung besser als im R?ntgenbild beobachtet werden. Das MRT-Signal war 5mal normal, 2mal partiell und einmal komplett pathologisch. Positives Hawkins-Zeichen und normales Signalverhalten sind prognostisch günstig zu werten. Es kam jedoch in Folge zentraler Talusfraktur auch bei radiologisch günstigem Verlauf zur Osteonekrose wenigstens von Teilen Talus gefolgt von schleichendem Ersatz. Die offenbar bei jeder zentralen Talusfraktur gest?rte Vaskularisation wurde von keinem radiologischen Befund einwandfrei reflektiert.      

Age and gender interactions on verbal memory performance.

Age and gender effects on verbal episodic memory are well established. However, the possibility of interactions between age and gender has been raised by studies linking estrogen and verbal memory performance, and by research suggesting gender differences in age-related cortical atrophy. We evaluated whether age by gender interactions in verbal memory were present. Subjects within three years of the median age of menopause were excluded from a large cohort of normal subjects, resulting in a younger sample (16-47 years) of 288 men and 285 women, and an older sample (55-89 years) of 201 men and 245 women. All subjects were administered the CVLT-2, a multiple-trial list-learning task. Verbal memory was negatively correlated with age for younger men, older men, and older women, but not for younger women. Multivariate analyses indicated age by gender interactions on memory for the younger group but not the older group. Results indicate that verbal memory declines with age for younger men but not younger women, whereas both older men and older women show age-related declines. These findings are consistent with hypotheses linking estrogen and verbal memory performance, and with imaging data suggesting that age-related hippocampal atrophy is found in younger men but not younger women. The role of estrogen on cognition in normal aging warrants further study.     

Mothers' and children's intakes of vitamin A in rural Bangladesh.

The vitamin A intake of 370 mothers and 183 children 3-27 mo of age in rural Bangladesh was ascertained monthly from January to July in 1986. For mothers, dark green leafy vegetables and fruits were the main sources of vitamin A. Vitamin A from vegetables, the single most important source, did not show consistent associations with wealth or with the other socioeconomic indicators. In May and June, fruits provided wealthier (and more educated) mothers with significantly higher vitamin A intakes than poor mothers, whereas in January the poorer mothers had higher intakes. When breast milk was included, average intakes for children came close to 100% of the recommended dietary allowance; the only other significant source of vitamin A for children was seasonally available mangoes. Fourteen children who had stopped breast-feeding by the end of the study were at very high risk of vitamin A deficiency when fruits were not plentiful.     

Progressive multifocal leukoencephalopathy in a lung transplant recipient.

Progressive multifocal leukoencephalopathy (PML) is a sub-acute, demyelinating disease of the brain caused by a human polyomavirus. We describe a patient with the onset of PML 7 months after lung transplantation. The patient was treated with immunosuppressive modulation and cidofovir, a new anti-viral therapy for PML, with stabilization of the symptoms. We also review the 4 additional reports in the literature of PML after heart and lung transplantation. Progressive multifocal leukoencephalopathy may become more prevalent as the population of heart and lung transplantation recipients increases.     

Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.