Acute cerebellar ataxia of a patient with SLE

We described a 28-year-old woman with systemic lupus erythematosus (SLE) presented with digestive tract, skin and renal symptoms and afterwards developed acute cerebellar ataxia, a paresis of the right inferior rectus muscle, left abducens paralysis and left facial palsy which seemed to be consistent with a brainstem lesion visible on magnetic resonance imaging (MRI). This lesion disappeared within 9 days of corticosteroid treatment. It is suggested that this lesion is focal edema induced by acute changes in the blood brain barrier secondary to a vasculopathy. Other causes, including local infarction, are unlikely.     

Light-induced phase-shifts in the circadian expression rhythm of mammalian period genes in the mouse heart

To investigate the molecular mechanism that regulates circadian rhythms in mammalian peripheral tissues, we examined the phase shifts evoked by light exposure in the circadian mRNA expression rhythms of mammalian Period genes (mPer1, mPer2 and mPer3) and a clock-controlled gene Dbp, in the mouse heart, by Northern blot analysis. The light pulse did not induce any acute mRNA expression of mPer in the heart, but the pulse gave rise to phase shifts in the circadian mRNA rhythms. On the first day after the exposure, only mPer1 mRNA showed a phase shift, whereas obvious phase shifts were not observed in the rhythms of mPer2, mPer3 and Dbp mRNAs. On the second day, phase shifts occurred to a similar extent in the mRNA rhythms of all four genes examined. The rhythm of mPer1 mRNA shifted fastest among those of the three mPers. Therefore mPer1 seems to play an important role in phase resetting of mammalian peripheral oscillators. Immediate responses to light pulses in mRNA expression of mPers may not be required for phase shifting of peripheral circadian oscillators. Our findings suggest that mammals require more than one day to have peripheral oscillators entrained to a new daily schedule.     

Hypothermia attenuates the vasodilatory response of pial arterioles to hemorrhagic hypotension in the cat

We investigated the effect of hypothermia on the vasodilatory response of pial arterioles to hemorrhagic hypotension. The cranial window technique was combined with microscopic video recording in an experiment involving 20 cats anesthetized with pentobarbital. The animals were randomly assigned to either a normothermic or a hypothermic group (32 degrees C). Mean arterial pressure (MAP) was reduced in stepwise increments of 10 mm Hg (from 100 to 50 mm Hg) by blood withdrawal. The diameter of small (50-100 microm) and large (100-200 microm) pial arterioles was measured. In the normothermic group (n = 9), small and large arterioles dilated at a MAP of 60 and 50 mm Hg, and at a MAP of 70, 60, and 50 mm Hg, respectively, compared with baseline values obtained at a MAP of 100 mm Hg. In contrast, in the hypothermic group (n = 11), vasodilation of either small or large arterioles was absent. The percentage diameter of small and large arterioles (percentage of control) was significantly lower at a MAP of 70, 60, and 50 mm Hg in the hypothermic group than the normothermic group. Our in vivo study demonstrates that hypothermia impairs autoregulatory vasodilation of pial arterioles in response to hemorrhagic hypotension. IMPLICATIONS: Deliberate mild hypothermia has been proposed as a means of providing cerebral protection during neurosurgical procedures. Our results suggest that cerebral blood flow autoregulation in response to hemorrhagic hypotension may be impaired during hypothermic conditions, indicating the importance of maintaining perfusion pressure during hypothermic therapy to prevent cerebral ischemia.     

A crucial role of uridine/cytidine kinase 2 in antitumor activity of 3'-ethynyl nucleosides.

The antitumor 3'-ethynyl nucleosides, 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine (EUrd), are potent inhibitors of RNA polymerases and show excellent antitumor activity against various human solid tumors in xenograft models. ECyd is being investigated in phase I clinical trials as a novel anticancer drug possessing a unique antitumor action. ECyd and EUrd require the activity of uridine/cytidine kinase (UCK) to produce the corresponding active metabolite. The UCK family consists of two members, UCK1 and UCK2, and both UCKs are expressed in many tumor cells. It was unclear, however, whether UCK1 or UCK2 is responsible for the phosphorylation of the 3'-ethynyl nucleosides. We therefore established cell lines that are highly resistant to the 3'-ethynyl nucleosides from human fibrosarcoma HT-1080 and gastric carcinoma NUGC-3. All the resistant cell lines showed a high cross-resistance to ECyd and EUrd. As a result of cDNA sequence analysis, we found that UCK2 mRNA expressed in EUrd-resistant HT-1080 cells has a 98-base pair deletion of exon 5, whereas EUrd-resistant NUGC-3 cells were harboring the point mutation at nucleotide position 484 (C to T) within exon 4 of UCK2 mRNA. This mutation was confirmed by genome sequence analysis of the UCK2 gene. Moreover, the expression of UCK2 protein was decreased in these resistant cells. In contrast, no mutation in the mRNA or differences in protein expression levels of UCK1 were shown in the EUrd-resistant HT-1080 and NUGC-3 cells. These results suggest that UCK2 is responsible for the phosphorylation and activation of the antitumor 3'-ethynyl nucleosides.     

Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients

Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of −34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (β = −0.3242, p = 0.0103) and peak serum trough level during TAC treatment (β = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation.     

Relationship of coffee consumption with a decline in kidney function among patients with type 2 diabetes: The Fukuoka Diabetes Registry

Aims/IntroductionThe evidence regarding the effects of coffee consumption on incident chronic kidney disease is inconclusive, and no studies have investigated the relationship in patients with diabetes. We aimed to prospectively investigate the relationship between coffee consumption and the decline in estimated glomerular function rate (eGFR) in patients with type 2 diabetes.Materials and MethodsA total of 3,805 patients (2,112 men, 1,693 women) with type 2 diabetes (mean age 64.2 years) and eGFR ≥60 mL/min/1.73 m² were followed (completion of follow up, 97.6%; median 5.3 years). Coffee consumption was assessed at baseline. The end‐point was a decline in eGFR to <60 mL/min/1.73 m² during the follow‐up period.ResultsDuring follow up, 840 participants experienced a decline in eGFR to <60 mL/min/1.73 m². Higher coffee consumption reduced the risk of decline in eGFR. Compared with no coffee consumption, the multivariate‐adjusted hazard ratios (95% confidence intervals) were 0.77 (0.63–0.93) for less than one cup per day, 0.77 (0.62–0.95) for one cup per day and 0.75 (0.62–0.91) for two or more cups per day (P for trend 0.01). This trend was unaffected by further adjustment for baseline eGFR and albuminuria. The mean eGFR change per year was −2.16 mL/min/1.73 m² with no coffee consumption, −1.89 mL/min/1.73 m² with less than one cup per day, −1.80 mL/min/1.73 m² with one cup per day and −1.78 mL/min/1.73 m² with two or more cups per day (P for trend 0.03).ConclusionsCoffee consumption is significantly associated with a lower risk of decline in eGFR in patients with type 2 diabetes.     

Medical visits of childhood cancer survivors in Japan: A cross‐sectional survey

Background: Although more children with cancer continue to be cured, these survivors experience various late effects. Details of the medical visit behaviors of childhood cancer survivors (CCS) in adulthood remain to be elucidated. Methods: In order to examine medical visits in the past and future of CCS, we performed a cross‐sectional survey with self‐rating questionnaires on medical visits of CCS compared with control groups (their siblings and the general population). Results: Questionnaires were completed by 185 CCS, 72 of their siblings and 1000 subjects from the general population and the results were analyzed. Mean ages at this survey and the duration after therapy completions of CCS were 23 and 12 years, respectively. We found that the previous treatment hospitals (where CCS were treated for their cancer) were the most commonly visited medical facilities for the CCS group (74% for female patients and 64% for male patients) and more than half of the CCS preferred to continue visiting the previous treatment hospital with enough satisfaction in Japan. The multivariate analysis showed that female sex and relapse were significantly associated with the past visits to the previous treatment hospital and that the CCS with brain tumors or bone/soft tissue sarcomas and CCS with any late effects tended to continue the relationships with the hospital. In addition female sex was also significantly associated with desired future visits to the previous treatment hospital. On the other hand, the married CCS tended to be disinclined to visit the hospital it in the future. Conclusions: In order to optimize risk‐based care and promote health for CCS after adulthood, we should discuss the medical transition with CCS and their parents.     

Colposcopic findings of gland openings in cervical carcinoma: their histological backgrounds

During the past 8 years 1501 colposcopies were performed paying a special attention to cervical glands for diagnosis of cervical intraepithelial neoplasia (CIN) and carcinoma. Normal openings could exclude these diseases at the error rate of only 5.1%, while atypical openings could identify them at the high confidence rate of 96.3%. False positive evaluations were mostly attributable to a marked degree of squamous metaplasia in the glands. The absence of gland openings in the main portion of the lesions amounted to 88.6% in invasive carcinomas but to only 12.4% in CIN. Adenoma malignum was a highly characteristic exception.     

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score–matched analysis

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score–matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.