Mixtures of human intermediate and human regular insulin in type 1 diabetic patients. Evaluation of free insulin levels and insulin action on glucose metabolism after combined and separate subcutaneous administration

Recent resorption studies in healthy subjects suggest that intermediate human zinc insulin preparations might diminish the absorption and activity of human short-acting insulin when the two insulins are administered as a single, combined preparation. This study was designed to investigate whether combined and separate administration of human zinc or human NPH insulin with soluble human insulin have different pharmacokinetic characteristics, as evaluated by glucose clamp studies and determination of free insulin levels. Eight type 1 diabetic patients received, in random order, four different, subcutaneously injected preparations of human insulin. Zinc insulin (Monotard HM, Novo-M) and protamine insulin (Protaphan HM, Novo-P) were each given with short-acting insulin (Actrapid HM, Novo-A). These insulins were administered either as a single combined preparation (MA;PA) or as two separate injections (M + A; P + A). Prior to the insulin injection euglycemia was achieved by an overnight intravenous insulin infusion. After the subcutaneous injection of insulin, glucose was monitored at 10-min intervals and euglycemia was maintained by a variable glucose infusion rate for 6 h. The total glucose infusion rate during this period was significantly lower following MA compared with M + A (total glucose infusion: 643 +/- 117 vs. 817 +/- 130 mg/kg, P = 0.009) whereas the glucose infusion rate did not differ between PA and P + A (878 +/- 122 vs. 914 +/- 118 mg/kg, NS(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk Factors for Hospitalizations Among Older Adults with Gastrointestinal Cancers

BackgroundOlder adults (≥65 years) with gastrointestinal (GI) cancers who receive chemotherapy are at increased risk of hospitalization caused by treatment-related toxicity. Geriatric assessment (GA) has been previously shown to predict risk of toxicity in older adults undergoing chemotherapy. However, studies incorporating the GA specifically in older adults with GI cancers have been limited. This study sought to identify GA-based risk factors for chemotherapy toxicity–related hospitalization among older adults with GI cancers.Patients and MethodsWe performed a secondary post hoc subgroup analysis of two prospective studies used to develop and validate a GA-based chemotherapy toxicity score. The incidence of unplanned hospitalizations during the course of chemotherapy treatment was determined.ResultsThis analysis included 199 patients aged ≥65 years with a diagnosis of GI cancer (85 colorectal, 51 gastric/esophageal, and 63 pancreatic/hepatobiliary). Sixty-five (32.7%) patients had ≥1 hospitalization. Univariate analysis identified sex (female), cardiac comorbidity, stage IV disease, low serum albumin, cancer type (gastric/esophageal), hearing deficits, and polypharmacy as risk factors for hospitalization. Multivariable analyses found that patients who had cardiac comorbidity (OR 2.48, 95% CI 1.13-5.42) were significantly more likely to be hospitalized.ConclusionCardiac comorbidity may be a risk factor for hospitalization in older adults with GI cancers receiving chemotherapy. Further studies with larger sample sizes are warranted to examine the relationship between GA measures and hospitalization in this vulnerable population.     

原发性高血压脑出血处理的新时代

文章着重讨论有关脑出血（ICH）处理方面的新认识和未来发展方向的最新报道。对高血压进行适当的治疗有可能预防ICH;对与ICH风险有关的微出血、载脂蛋白基因型和胆固醇的处理进行了探讨。血肿分解产物、基质金属蛋白酶、炎症标记物以及减轻损伤的方法也给予了关注。对血肿周围水肿多方面的特征做了进一步的定义,但对血肿周围缺血的证据仍难以捉摸。有关急性期血压的最新资料增强了进行临床试验的需要。由于一项里程碑式的外科手术试验——国际脑出血外科手术试验（International Surgical Trial in Intra-cerebral Hemorrhage,ISTICH）发现,外科手术缺乏疗效．因此重点正在转向微创和基于导管／溶栓技术清除血块。在内科治疗方面,研究已经表明活化的Ⅶ因子可控制血肿增大。展望未来,ICH的干细胞治疗正在研究之中,一些转归研究正在展现出新的希望。     

Multidetektor-Computertomographie bei Neurologischen Notfällen

Computed tomography (CT) is one of the most important methods for imaging diagnostics together with magnetic resonance imaging (MRI) for direct detection of localized or diffuse processes in the brain and spinal cord. Although MRI is superior for visualization of intracranial soft tissue contrast, CT plays an indispensible role in emergency diagnostics due to the wide availability and recent developments in radiological equipment techniques. The short examination time, better surveillance possibilities for severely ill patients and better assessment of bony structures are only some of the advantages of CT. New generation CT scanners, so-called multidetector computed tomographs allow examinations using the spiral technique due to high performance tubes as well as hardware and software modifications. Especially in cranial imaging three-dimensional reconstructions are possible and artefacts can be minimized. Additionally vessel imaging is possible using contrast-enhanced CT angiography due to the short scanning time, which after 3-D reconstruction supplies a mobile image of vessels suitable for screening for aneurysms and occlusions. The rapid injection of iodine-containing contrast media results in images free from flow phenomena in contrast to MR angiography. Even assessment of blood permeation of an organ such as the brain is possible using dynamic perfusion-weighted imaging CT (PWI-CT). The clinical importance lies for example in the assessment of indications for rapid recanalization in cases of acute insults. The clinical picture in neurological emergencies can be influenced by a multitude of intracranial and intracerebral processes. With CT, radiology offers a rapid and nowadays often decisive support for a differential diagnosis by clinicians.     

Initiation of and adherence to treatment for mental disorders: examination of patient advocate group members in 11 countries

OBJECTIVE: Greater understanding of the help-seeking process is needed to reduce the level of unmet need for mental health treatment. DESIGN: Cross-sectional mail survey. STUDY POPULATION: The study population consisted of 3,516 respondents to a survey of members of 14 patient advocacy groups in 11 countries. Respondents reported whether they initiated and adhered to the treatment most recently recommended to them. OUTCOMES: Crude and adjusted likelihoods of initiating and adhering to recommended treatment were studied. RESULTS: The vast majority of respondents reported initiating the most recent treatment recommended to them (94%), and most of those who initiated treatment also adhered to such treatment (83%). Predictors of initiation by the respondents included higher levels of education, having pharmacotherapy recommended to the respondent, and having received explanations about the diagnosis and treatment. Predictors of adherence to therapy included male gender, receipt of pharmacotherapy, and presence of insurance coverage. Side effects were an important reported reason for treatment dropout, with 44% of respondents reporting lifetime treatment dropout due to side effects. CONCLUSIONS: Successful initiation and adherence to mental health treatments depend critically on patients' knowledge and awareness, clinicians' communication skills, treatment side effects, and barriers such as lack of insurance. Further study and intervention focused on these modifiable factors are needed to improve the adequacy of mental health treatment.     

Using machine learning classifiers to identify glaucomatous change earlier in standard visual fields

PURPOSE: To compare the ability of several machine learning classifiers to predict development of abnormal fields at follow-up in ocular hypertensive (OHT) eyes that had normal visual fields in baseline examination. METHODS: The visual fields of 114 eyes of 114 patients with OHT with four or more visual field tests with standard automated perimetry over three or more years and for whom stereophotographs were available were assessed. The mean (+/-SD) number of visual field tests was 7.89 +/- 3.04. The mean number of years covered (+/-SD) was 5.92 +/- 2.34 (range, 2.81-11.77). Fields were classified as normal or abnormal based on Statpac-like methods (Humphrey Instruments, Dublin, CA) and by several machine learning classifiers. The machine learning classifiers were two types of support vector machine (SVM), a mixture of Gaussian (MoG) classifier, a constrained MoG, and a mixture of generalized Gaussian (MGG). Specificity was set to 96% for all classifiers, using data from 94 normal eyes evaluated longitudinally. Specificity cutoffs required confirmation of abnormality. RESULTS: Thirty-two percent (36/114) of the eyes converted to abnormal fields during follow-up based on the Statpac-like methods. All 36 were identified by at least one machine classifier. In nearly all cases, the machine learning classifiers predicted the confirmed abnormality, on average, 3.92 +/- 0.55 years earlier than traditional Statpac-like methods. CONCLUSIONS: Machine learning classifiers can learn complex patterns and trends in data and adapt to create a decision surface without the constraints imposed by statistical classifiers. This adaptation allowed the machine learning classifiers to identify abnormality in visual field converts much earlier than the traditional methods.     

Electrocardiographic changes at the onset of epileptic seizures

PURPOSE: We studied heart-rate (HR) changes at the transition from the preictal to the ictal state in patients with focal epilepsies to gain some insight into the mechanisms involved in the neuronal regulation of cardiovascular function. METHODS: We assessed ECG changes during 145 seizures recorded with scalp EEG in 58 patients who underwent video-EEG monitoring. Consecutive RR intervals were analyzed with a newly developed mathematical method for a total of 90 s. RESULTS: Ictal-onset tachycardia occurred in 86.9% of all seizures, whereas bradycardia was documented only in 1.4%. The incidence as well as the amount of ictal HR increase was significantly more pronounced in patients with mesial temporal lobe epilepsy (TLE) as compared with those with non-lesional TLE or extratemporal epilepsy. Moreover, right hemispheric seizures were associated with ictal-onset tachycardia. On average, ictal HR increase preceded EEG seizure onset by 13.7 s in TLE patients and 8.2 s in patients with extratemporal epilepsy. This difference was significant. Ictal HR changes could be classified according to their temporal evolution into two different patterns. These two patterns differed significantly between the temporal lobe and the extratemporal epilepsy patient group. CONCLUSIONS: Epileptic discharges directly influence areas of the central autonomic network, thus regulating HR and rhythm. Such changes occur before ictal discharges appear on surface electrodes. Our newly developed method may be of potential use for clinical applications such as automatic seizure-detection systems. Moreover, our method might help to clarify further the basic mechanisms of interactions between heart and brain.