Pachymeningitis with pseudo-Foster Kennedy syndrome

PURPOSE: To report a case of pachymeningitis with pseudo-Foster Kennedy syndrome in a patient who was positive for perinuclear antineutrophil cytoplasmic antibody. METHODS: Case report. A 44-year-old man was examined for headache and diplopia. RESULTS: Left eye showed limitation of abduction. Ocular fundus, computed tomography (CT), and magnetic resonance imaging (MRI) of the head and orbits were normal. The diplopia subsided spontaneously. Six months later, he noticed sudden visual loss in the left eye. The left eye showed optic disk atrophy and episcleritis, and the right eye showed papilloedema. Computed tomography and MRI exhibited thickened dura mater. Serum perinuclear antineutrophil cytoplasmic antibody level was highly increased. CONCLUSION: Pachymeningitis with ocular involvement sometimes requires repeated CT or MRI for diagnosis. This disorder may be caused by microvasculitis.     

Characterization and effects of methyl-2- (4-aminophenyl)-1, 2-dihydro-1-oxo-7- (2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), a novel potent inhibitor of cGMP-binding cGMP-specific phosphodiesterase (PDE5)

An isoquinolone derivative, methyl-2-(4-aminophenyl)-1, 2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), was found to be a novel potent inhibitor of cyclic GMP (cGMP)-binding cGMP-specific phosphodiesterase (PDE5). We investigated the inhibitory effects of T-1032 on six PDE isozymes isolated from canine tissues. T-1032 specifically inhibited the hydrolysis of cGMP by PDE5 partially purified from canine lung, at a low concentration (IC(50) = 1.0 nM, K(i) = 1.2 nM), in a competitive manner. In contrast, the IC(50) values of T-1032 for PDE1, PDE2, PDE3, and PDE4 were more than 1 microM. T-1032 also inhibited PDE6 from canine retina with an IC(50) of 28 nM, which is of the same order of magnitude as the IC(50) of sildenafil. cGMP hydrolytic activities of two alternative splice variants of canine PDE5 expressed in COS-7 cells were inhibited by this compound to a similar extent. T-1032 increased the intracellular concentration of cGMP in cultured rat vascular smooth muscle cells in the presence and absence of C-type natriuretic peptide, an activator of membrane-bound guanylate cyclase, whereas the compound did not change cyclic AMP levels. These data indicated that T-1032, which belongs to a new structural class of PDE5 inhibitors, is a potent and selective PDE5 inhibitor. This compound may be useful in pharmacological studies to examine the role of a cGMP/PDE5 pathway in tissues.     

Cholinergic dysfunction in cognitive impairments after aneurysmal subarachnoid hemorrhage

OBJECTIVE: Although cognitive impairments have been observed after subarachnoid hemorrhage (SAH), little is known about their neurobiological bases. To examine cholinergic function in such patients, we used a known test for Alzheimer's disease based on an exaggerated pupil dilation response to a cholinergic antagonist, tropicamide (the tropicamide drop test). METHODS: Seventeen patients who were treated surgically after aneurysmal SAH were divided into two groups on the basis of their scores on the Mini-Mental State Examination (MMSE): Group A (MMSE > or =28) and Group B (MMSE < or =27). The mean interval of time between surgery and administration of the MMSE was 4.7 +/- 2.1 years for Group A and 4.2 +/- 1.3 years for Group B. The tropicamide drop test was performed within 1 month after the MMSE for each patient. After measurement of the baseline pupil diameter (R1, right pupil size: L1, left pupil size), one drop of 0.01% tropicamide was applied to the right eye and physiological saline to the left eye. Pupil diameter (R2, right pupil size; L2, left pupil size) was then remeasured. Data were represented as the dilation ratio of the right pupil (R2/R1) and as the relative dilation ratio of the right pupil to that of the left pupil (R2L1/R1L2). RESULTS: The mean dilation ratio of the right pupil (R2/R1) was higher in Group B (1.13 +/- 0.09) than in Group A (1.07 +/- 0.11), although the difference did not reach statistical significance (P = 0.18). The relative dilation ratio (R2L1/R1L2) was significantly higher in Group B (1.41 +/- 0.36) than in Group A (1.06 +/- 0.20) (P < 0.05). CONCLUSION: We determined cholinergic dysfunction in patients with cognitive impairment after SAH on the basis of the pupillary response to tropicamide. The results provide an insight into the pathophysiology of cognitive impairments after SAH, which might lead to future treatment strategies.     

Successful treatment with 5-fluorouracil of conjunctival intraepithelial neoplasia refractive to mitomycin-C

PURPOSE: To describe the histopathological findings and successful treatment with 5-fluorouracil (5-FU) of a conjunctival intraepithelial neoplasia with limbal stem cell deficiency that was refractive to topical mitomycin-C (MMC). DESIGN: Interventional case report. INTERVENTION: A 64-year-old male patient presented with a diffuse conjunctival intraepithelial neoplasia (CIN) that was excised with concurrent keratoepithelioplasty. Because of a recurrence and the presence of limbal stem cell deficiency, he was placed on topical MMC. Despite two courses of MMC, the tumor size did not decrease, and topical 5-FU was started 1 year after MMC therapy began. Limbal autograft transplantation was performed thereafter. MAIN OUTCOME MEASURES: The clinical and histopathologic findings including impression cytology and biomicroscopic observations. RESULTS: After 5-FU treatment, the patient was free of the tumor clinically and cytologically, and the corneal surface had cleared. No recurrence was observed during the 30 months after the 5-FU therapy. Serious complications have not been observed. CONCLUSIONS: Topical 5-FU may be a therapeutic option for the treatment of patients with MMC-resistant CINs. The success of 5-FU is believed to be the result of a difference in the mechanism of cytotoxicity of MMC and 5-FU or the additive effects of the two agents.     

Twenty-six week carcinogenicity study of ampicillin in CB6F1-TgrasH2 mice

As a part of the ILSI-HESI Alternative to Carcinogenicity Testing (ACT) program, we performed a 26-week carcinogenetic study of nonmutagenic drug, ampicillin (ABPC) in Tg-rasH2 mice. ABPC was given to Tg-rasH2 mice (0, 350, 1000, 3000 mg/kg, p.o.) and Non-Tg mice (0, 3000 mg/kg, p.o.) daily for 26 weeks. As a positive control, a single dose of MNU was administered once to Tg-rasH2 mice (75 mg/kg, i.p.). In this study, Tg-rasH2 mice did not demonstrate any increases in tumor development in response to ABPC. Thus, ABPC had no carcinogenicity in the 26-week carcinogenesis study in Tg-rasH2 mice or in a 2-year carcinogenesis study in B6C3F1 mice.     

Uptake of FH by two types of scavenger-like receptors in rat liver parenchymal cells in primary culture

Several anionic proteins that are known to be substrates of scavenger receptors documented in the literature were selected and tested for their effects on the uptake of fractionated heparin (FH), an anionic macromolecular drug. The tests were made in rat liver parenchymal cells to characterize scavenger-like receptors involved in FH uptake, probing into substrate recognition characteristics in comparison with those of scavenger receptors. Although the uptake of FH was completely inhibited by dextran sulfate, a typical substrate of scavenger receptors, suggesting that scavenger-like receptors that have affinity for some anionic macromolecules are responsible for the uptake, it was not inhibited by acetylated low density lipoprotein (Ac-LDL), another typical substrate. Thus, the scavenger-like receptors were suggested to be different from the major scavenger receptors of classes A and B that are known to be sensitive to Ac-LDL. The uptake of FH was only partially inhibited by maleylated bovine serum albumin (Mal-BSA), suggesting that the scavenger-like receptors can be classified into two types in terms of sensitivity to Mal-BSA. The Mal-BSA-sensitive receptor was also found to be sensitive to oxidized low density lipoprotein (Ox-LDL). Kinetic analysis revealed that the binding capacity (Bmax) of the Mal-BSA-insensitive receptor was significantly larger than that of the Mal-BSA-sensitive one, though their dissociation constants (Kd) and apparent internalization rate constants (kint,app) were comparable. Information obtained in this study should be helpful for understanding the disposition mechanism of FH and also of anionic macromolecules and for developing delivery strategies, although the physiological roles and molecular identity of each receptor need to be further clarified in the future.     

Cognitive conditions of pathologically confirmed dementia with Lewy bodies and Parkinson's disease with dementia

The relationship between dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) has been insufficiently described, and it is still problematic. Twenty-nine cases of DLB and 10 cases of PDD were investigated in the present study. DLB cases disclosed a significantly older disease onset and shorter disease duration than PDD cases (p<0.01 each). However, they showed no significant difference in dementia onset or dementia duration (p>0.05 each). Motor symptoms (parkinsonism) were suspected as the cause of the younger disease onset in PDD cases. Compared with 10 age-matched cases of definite Alzheimer's disease, both 19 DLB cases and 6 PDD cases had significantly better scores in the final test of mini-mental state examination (MMSE) and revised version of Hasegawa's Dementia Scale (HDSR) within 12 months before death, although no significant differences between DLB and PDD were indicated. DLB and PDD were suspected to show cognitive impairment of similar severity in the terminal stage. They would thus be difficult to classify as completely different entities.     

Death in epilepsy with special attention to suicide cases

To examine clinical features of cases of death among epilepsy patients as a case-control study, with special attention to suicide, we analyzed the records of 43 deceased patients with well-classified epilepsy. The subjects were compared with 1,722 control patients who showed definite subtypes of epilepsy. As a result, among the major causes of death, 13 of the subjects suffered accidents (mostly drowning), ten experienced sudden unexpected death, seven had status epilepticus, and six committed suicide. There were no significant differences with regard to clinical variables except for psychotic episodes, which were more frequently encountered in subjects than in controls (chi(2)=6.771, P=0.009, Yates' modification). Statistically significant differences were found by epilepsy type as well (chi(2)=14.72, P=0.002), with temporal lobe epilepsy (TLE) proving to be most closely associated with death among the epilepsy patients. Further, suicide was only encountered in patients with TLE and the association was statistically significant (chi(2)=5.119, P=0.024). Half of those who committed suicide (n=3), did so by jumping in front of an oncoming train while in the midst of an episode of postictal psychosis. In conclusion, most cases of suicide in patients with epilepsy were found to be the result of an immediate causal relationship with ictal or interictal epileptic manifestations, rather than a result of augmentation of psychosocial stressors generated by a long-standing handicap derived from the severe illness.