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Recent advances in developing disease-modifying therapies (DMT) for Alzheimer's disease (AD), and the recognition that AD pathophysiology emerges decades before clinical symptoms, necessitate a paradigm shift of health-care systems toward biomarker-guided early detection, diagnosis, and therapeutic decision-making. Appropriate incorporation of cerebrospinal fluid biomarker analysis in clinical practice is an essential step toward system readiness for accommodating the demand of AD diagnosis and proper use of DMTs-once they become available. However, the use of lumbar puncture (LP) in individuals with suspected neurodegenerative diseases such as AD is inconsistent, and the perception of its utility and safety differs considerably among medical specialties as well as among regions and countries. This review describes the state-of-the-art evidence concerning the safety profile of LP in older adults, discusses the risk factors for LP-associated adverse events, and provides recommendations and an outlook for optimized use and global implementation of LP in individuals with suspected AD.

BACKGROUND We studied the relationship between the recurrence rate of primary superficial bladder cancer and random biopsy. METHODS We performed transurethral resection of primary superficial bladder cancer in 144 patients, and in 55 of those cases a random biopsy was also performed. The non-recurrence rate was examined in many recurrence facters. RESULTS The non-recurrence rate in the group with random biopsy was not significantly different from that observed in the group (100 patients) without random biopsy (chi 2 test, Generalized Wilcoxon test and multivariate analysis). Because the intravesical instillation therapy is an important inhibition factor in the recurrence rate of the primary superficial bladder cancer, we further analysed the recurrence rate in two non treated groups with or without random biopsy (13 and 35 patients respectively). No significant difference in the rate of recurrence between the two groups was observed. However, we noted recurrence of bladder cancer at biopsy positions in 8/13 patients. CONCLUSION It appears that random biopsy may have an effect on the recurrence or the implantation of tumor cells. Further studies are needed to clarify whether random biopsy is a risk factor in the recurrence rate of primary superficial bladder cancer.

尿路感染症に対するIPM/CSの臨床効果を尿管皮膚瘻造設術を受けた19例の悪性腫瘍患者(膀胱腫瘍15例, 前立腺癌3例, 子宮癌1例)について観察した.IPM/CSの投与法は1回0.5 gを1日2回点滴静注し, 薬効評価は投与後5日目にUTI判定基準に従って行った.その結果, 総合臨床効果は著効4例(20.0%), 有効9例(45.0%), 無効7例(35.0%)で総合有効率は65.0%となった.疾患病態群別にみた効果は, G-3群(単独菌感染・上部尿路感染)が3例で有効率は33.0%, G-6群(複数菌感染・カテーテル非留置)が17例で有効率は70.6%であった.細菌学的効果としては, 分離菌38株中34株が本剤投与後に消失し, 消失率は89.5%であった, Clinical efficacy of IPM/CS against urinary tract infections (UTI) was evaluated on 19 patients with malignancies (bladder tumor: 15, prostate cancer: 3, uterus cancer: 1) and 1 patient with a benign disorder (ureter stenosis) who had undergone ureterocutaneostomy between January, 1988 and December, 1990. Their ages ranged from 42 to 79 years. Postoperatively, they had UTI with pyuria of greater than or equal to 5/hpf and bacteriuria of greater than or equal to 10(4)/ml. IPM/CS was administered at a dose of 0.5 g (0.25g/0.25 g) twice a day through intravenous drip infusion. Its efficacy was evaluated according to the UTI criteria for clinical evaluation as ruled by the Japanese Society of Chemotherapy. Overall clinical value was rated "excellent" in 4 (20%), "moderate" in 9 (45%) and "poor" in 7 (35%) cases for a total of 65%. The efficacy by types of infection was 33% and 70.6% in the group of single infection and in the group of mixed infection, respectively. As to bacteriological efficacy 34 of the 38 strains (89.5%) isolated were eradicated following its administration. The eradication rate was 84.6% for P. aeruginosa, and 84.6% for E. faecalis. Microbes which appeared after its dosing amounted to 6 classes of 17 strains, 6 NFB strains of which were identified. As a side effect, elevation of serum GPT (5%) was noted. Regardless of the underlying conditions (malignant diseases and ureterocutaneostomy), clinical efficacy of IPM/CS was appreciable. In addition, the MIC for (P. aeruginosa, E. faecalis) of IPM/CS was lower than that of PIPC.

Endotoxaemia was investigated by the Limulus assay in 42 cirrhotic patients with ascites and in 33 without ascites. The incidence of endotoxaemia in the former group (59.5%) was significantly (P less than 0.05) higher than in the latter (36.4%). Correlation between endotoxaemia and specific gravity and concentrations of total protein, albumin, and globulin in ascitic fluid was studied in the group with ascites. The specific gravity of ascites in 25 patients with endotoxaemia was significantly greater than that in 17 patients without endotoxaemia (P less than 0.01). The concentration of total protein in patients with endotoxaemia (13.95 +/- 7.18 milligram, mean +/- SD) was nearly twice as high (P less than 0.01) as in patients without endotoxaemia (7.49 +/- 3.60 milligram). The protein content of those who showed reactions greater or equal to 2(+) in the Limulus assay (16.78 +/- 7.14 milligram) was a significantly (P less than 0.05) higher than in those with 1(+) reaction (11.26 +/- 6.33 milligram). Moreover, the concentration of albumin in patients with endotoxaemia (7.68 +/- 4.60 milligram) was more than twice that of the patients without endotoxaemia (3.39 +/- 1.58 milligram, P less than 0.01). On the other hand, globulin concentration in patients with endotoxaemia was 1.6 times that of patients without endotoxaemia (P less than 0.01). Similar differences were noted between endotoxaemic and non-endotoxaemic patients in the ascites-to-serum ratio in protein, albumin, and globulin. These results suggest that in liver cirrhosis endotoxaemia may cause an increase in protein concentrations in ascitic fluid, and that it may be a precipitating factor in the formation of ascites.

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease caused by unstable expansion of a CAG repeat in the DRPLA gene. We performed detailed quantitative analysis of the size and the size distribution (range) of the expanded CAG repeats in various regions of the CNS of eight autopsied patients with DRPLA. Expanded alleles (AE) showed considerable variations in size, as well as in range, depending on the region of the CNS, whereas normal alleles did not show such variations, which indicates the occurrence of somatic mosaicism of AE in the CNS. The AE in the cerebellar cortex were consistently smaller by two to five repeat units than those in the cerebellar white matter. Moreover, the AE in the cerebral cortex were smaller by one to four repeat units than those in the cerebral white matter. These results suggest that the smaller AE in the cerebellar and cerebral cortices represent those of neuronal cells. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter showed considerable variation ranging from 9 to 23 repeat units, whereas those in the cerebellar cortex showed little variance and were approximately 7 repeat units. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter were much broader in patients with higher ages at death than they were in patients with lower ages at death, raising the possibility that the range of AE increases with time, as the result of mitotic instability of AE.