Olfactory Absorption of Insulin to the Brain

A vast number of potent neuropharmaceuticals, many of which are peptides, are excluded from entry into the brain because of the highly selective blood-brain barrier. The fact that a number of drugs have been shown to be transported directly to the central nervous system following application to the olfactory region of the nose is therefore of major interest. In the present study, the feasibility of delivering peptides to the brain via the olfactory route was assessed using insulin as a model peptide. Systemic hyperinsulinemia induced by subcutaneous injection did not significantly reduce the amount of ¹²⁵I-insulin transported from the nose to the brain in vivo, which suggests that the impact of systemic absorption on drug transport is minimal. A linear relationship was seen between insulin accumulation in the brain and the dose applied, without any relevant saturation. Contrary to what was expected, both systemic and olfactory absorption of insulin was enhanced when the pH of the medium was near the isoelectric point. The amount absorbed to the brain was found to be linearly related to the net charge of the molecule (r = -0.61; n = 20). It was concluded that insulin gains access to the central nervous system from the olfactory region of the nose by a nonspecific pathway. The olfactory route may therefore become an important means to deliver peptides to the brain.     

Compartment syndrome. Exclusively the result of increased pressure in the muscular compartment?

Summary The compartment syndrome (cs) is characterized by an increased tissue pressure in a limited space. Pathophysiologically, it is a multifactorial disease that is potentially induced by an initial trauma and develops according to the existence of cofactors. Cofactors are, for instance, the circulation of the patient and the initial treatment of the impending cs. In particular, the microcirculation is altered with endothelial destruction, development of a capillary leak, protein loss from intravasal space and the development of an interstitial and intracellular third space. An impaired drainage of the lymphatic and venous system causes a venous infarction. An arterial infarction results if the tissue pressure exceeds the arteriolar pressure. An accompanying ischemia reperfusion mechanism increases the trauma load. In disadvantageous cases, the patients are in danger of developing a multi-organ deficiency syndrome (MODS) by an uncontrolled inflammatory reaction, by intravasal volume loss and by a myonephropathic systemic reaction. Clinically, the patients suffer a disproportionate amount of pain, followed by neurological signs. Especially in noncompliant patients, tissue pressure measurement is useful. Resuscitation of the circulation as well as splitting of casts is important. In case of a manifest cs, dermatofasciotomy has to be performed as an emergency operation. Even if cs is diagnosed early and fasciotomy is carried out early, the development of sequellae cannot be avoided in every single case.      

Toluene in blood as a marker of choice for low-level exposure to toluene

The validity of two new biological exposure markers of toluene in blood (TOL-B) and toluene in urine (TOL-U) was examined in comparison with that of the traditional marker of hippuric acid in urine (HA-U) in 294 male workers exposed to toluene in workroom air (TOL-A), mostly at low levels. The exposure was such that the geometric mean for toluene was 2.3 ppm with a maximum of 132 ppm; the workers were also exposed to other solvents such as hexane, ethyl acetate, styrene, and methanol, but at lower levels. The chance of cutaneous absorption was remote. Higher correlation with TOL-A and better sensitivity in separating the exposed workers from the nonexposed subjects were taken as selection criteria. When workers exposed to TOL-A at lower concentrations (< 50 ppm, < 10 ppm, < 2 ppm, etc.) were selected and correlation with TOL-A was examined, TOL-B showed the largest correlation coefficient which was significant even at TOL-A of < 1 ppm, whereas correlation of HA-U was no longer significant when TOL-A was < 10 ppm. TOL-U was between the two extremes. The sensitivities of TOL-B and TOL-U were comparable; HA-U showed the lowest sensitivity. Thus, it was concluded that TOL-B is the indicator of choice for detecting toluene exposure at low levels.     

声音振动刺激试验在临床上的应用

应用声振仪对１９９２年２个月～１９９３年６个月单胎３６～４３周妊娠孕妇１５０例进行了声音振动刺激试验（ＶＡＳ－Ｔ）并与无负荷试验（ＮＳＴ）对照。对此结果ＶＡＳ－Ｔ（＋）１４６例，（－）４例，ＮＳＴ反应型９６例，无反应型５４例。ＮＳＴ无反应型预测价值８％，假阴性率９２％。ＮＳＴ无反应型经声音刺激后５０例成ＶＡＳ－Ｔ（＋）。ＶＡＳ－Ｔ预测价值９９．３％。ＮＳＴ有效率６６％，ＶＡＳ－Ｔ有效率９９％。ＮＳＴ至少需做２０ｍｉｎ，ＶＡＳ－Ｔ９５％在３ｍｉｎ内达到标准，最长１５ｍｉｎ。为避免ＮＳＴ假无反应型，应进行ＶＡＳ－Ｔ。     

A neuromuscular monitoring system based on a personal computer

We have developed a computerized neuromuscular monitoring system (NMMS) using commercially available subsystems, i.e., computer equipment, clinical nerve stimulator, force transducer, and strip-chart recorder. This NMMS was developed for acquisition and analysis of data for research and teaching purposes. Computer analysis of the muscle response to stimulation allows graphic and numeric presentation of the twitch response and calculated ratios. Since the system can store and recall data, research data can be accessed for analysis and graphic presentation. An IBM PC/AT computer is used as the central controller and data processor. The computer controls timing of the nerve stimulator output, initiates data acquisition, and adjusts the paper speed of the strip chart recorder. The data processing functions include establishing control response values (when no neuromuscular blockade is present), displaying force versus time and calculated data graphically and numerically, and storing these data for further analysis. The general purpose nature of the computer and strip chart recording equipment allow modification of the system primarily by changes in software. For example, new patterns of nerve stimulation, such as the posttetanic count, can be programmed into the computer system along with appropriate data display and analysis routines. The NMMS has functioned well in the operating room environment. We have had no episodes of electrocautery interference with the computer functions. The automated features have enhanced the utility of the NMMS. The prime advantages of this system are (1) the ability to customize its features by altering its controlling programs, (2) the ready availability of the hardware and software, (3) the general purpose nature of the system, so that it is not limited to this one application, and (4) the adaptable nature of the system.     

Multiplex PCR analysis of in vivo-arising deletion mutations in the hprt gene of human T-lymphocytes

A multiplex polymerase chain reaction (PCR) procedure was adapted for the rapid and efficient evaluation of deletions of the hypoxanthine guanine phosphoribosyltransferase (hprt) gene in human T-lymphocytes. The hprt clonal assay was used to isolate in vivo-arising hprt-deficient T-cells from six healthy males. Mutant frequencies ranged from 9-27 × 10^?6. Simple crude cellular extracts from 223 mutants were analyzed for hprt gene deletion. Sixteen (7.2%) were found to be due to total gene deletion and 22 (9.9%) were due to partial gene deletion. The relatively high frequency of total gene deletions was caused by replicate isolates of a single mutational event as shown by single-strand conformation polymorphism (SSCP) analysis of rearranged T-cell receptor (TCR)-γ genes. Eighteen of the 22 partial hprt gene deletion mutants were determined to be of independent origin based on a unique hprt mutation or SSCP-TCR-γ pattern. One-half (9/18) of the partial deletion mutants involved all or part of exon 4 alone, suggesting that this region of the hprt gene is prone to deletion. The small deletions effecting exon 1 (1 mutant), exon 2 (2 mutants), and exon 4 (6 mutants) would not have been detected by conventional Southern blot analysis and may represent a new, previously unrecognized class of mutations. The ready isolation of such intragenic deletions will allow the characterization of breakpoint junctions and may provide insights into the important processes of DNA breakage and rejoining. © 1994 Wiley-Liss, Inc.     

End-tidal Carbon Dioxide Monitoring during Procedural Sedation

OBJECTIVE: To prospectively determine whether end-tidal carbon dioxide (ETCO2) monitors can detect respiratory depression (RD) and the level of sedation in emergency department (ED) patients undergoing procedural sedation (PS). METHODS: This was a prospective observational study conducted in an urban county hospital of adult patients undergoing PS. Patients were monitored for vital signs, depth of sedation per the physician by the Observer's Assessment of Alertness/Sedation scale (OAA/S), pulse oximetry, and nasal-sample ETCO2 during PS. Respiratory depression was defined as an oxygen saturation <90%, an ETCO2 >50 mm Hg, or an absent ETCO2 waveform at any time during the procedure. The physician also determined whether protective airway reflexes were lost during the procedure and assisted ventilation was required, or whether there were any other complications. Rates of RD were compared with the physician assessment of airway loss and between agents using chi-square statistics. Spearman's rho analysis was used to determine whether there was a correlation between ETCO2 and the OAA/S score. RESULTS: Seventy-four patients were enrolled in the study. Forty (54.1%) received methohexital, 21 (28.4%) received propofol, ten (13.5%) received fentanyl and midazolam, and three (4.1%) received etomidate. Respiratory depression was seen in 33 (44.6%) patients, including 47.5% of patients receiving methohexital, 19% receiving propofol (p = 0.008), 80% receiving fentanyl and midazolam, and 66.6% receiving etomidate. No correlation between OAA/S and ETCO2 was detected. Eleven (14.9%) patients required assisted ventilation at some point during the procedure, all of whom met the criteria for RD. Pulse oximetry detected 11 of the 33 patients with RD. Post-hoc analysis revealed that all patients with RD had an ETCO2 >50 mm Hg, an absent waveform, or an absolute change from baseline in ETCO2 >10 mm Hg. CONCLUSIONS: There was no correlation between ETCO2 and the OAA/S score. Using the criteria of an ETCO2 >50 mm Hg, an absolute change >10 mm Hg, or an absent waveform may detect subclinical RD not detected by pulse oximetry alone. The ETCO2 may add to the safety of PS by quickly detecting hypoventilation during PS in the ED.     

Preparation and evaluation of temperature sensitive liposomes containing adriamycin and cytarabine

Temperature sensitive liposomes (TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drugs. Lipid compositions of TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition temperature (T_c) of TSL was dependent on the lipid compositions of TSL.ADM broadened thermogram of TSL but Ara-C did not. However, T_c of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near T_c and observed at 39–41°C for DPPC (Dipalmitoylphosphatidylcholine) only, 52–54°C for DSPC (Distearoylphosphatidylcholine) only, 41–43°C for DPPC and DSPC (3∶1), and 43–45°C for DPPC and DSPC (1∶1), respectively. Effect of human serum albumin (HSA) on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below T_c. However, ADM release from TSL was increased at the near and above T_c. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near T_c. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at 4°C was not changed, the TSL was considered to be stable for at least 1 week at 4°C. Based on these findings, TSL may be useful to deliver drugs to preheated target sites due to its thermal behaviors.     

运动员Marfan氏综合征的医务监督

目的 :提高教练员和医生对Marfan氏综合征的认识 ,更好地预防运动性猝死。同时为掌握身材高大项目运动员身体形态测量的规律提供参考数据。方法 :通过对 4例确诊和疑似马凡氏综合征运动员从疾病发现、发展变化、死亡、转归过程的阐述、分析 ,提供了对确诊和疑似马凡氏综合征运动员的处理、治疗方案及注意事项。同时对现役国家男、女篮球队运动员进行了包括眼科、骨科、心电图、超声心动图等全面的体检 ,以排查马凡氏综合征。结果提示 :男性运动员主动脉根部大于 60mm、女性大于 5 0mm已具有猝死风险 ,应给予高度重视。篮球运动员臂展 >身高者占4 3 3% ,且男性臂展 /身高 >1 0 3者占 2 0 %。     

Facilitating access to glucometer reagents increases blood glucose self-monitoring frequency and improves glycaemic control: a prospective study in insulin-treated diabetic patients.

AIMS: To investigate whether availability of glucometer reagents increases the frequency of self-blood glucose monitoring (SBGM) and improves glycaemic control in diabetic patients. METHODS: Sixty-two insulin-treated diabetic patients were randomized to two groups, matched for age, gender, education, income, type and duration of diabetes, years of insulin treatment, number of daily insulin injections, and haemoglobin (Hb)A1c. All patients were given a glucometer, but one group (no cost, NC) was provided glucometer test strips free of charge. The other group (control, C) had to purchase strips as they found it necessary. Both groups of patients were followed longitudinally at 2-monthly intervals for 12 months with measurement of blood glucose and HbA1c, and the frequency of SBGM was determined by downloading the glucometer memory. RESULTS: The SBGM frequency was significantly higher in the NC group vs. the C group during the first 4 months (2.0 +/- 0.2 tests/day vs. 1.4 +/- 0.1 tests/day, P<0.025). Mean HbA1c remained stable over the 12 months in the NC group, whereas an increase with time was observed in the C group. The difference in HbA1c between the two groups was significant (P<0.002) after 6 months. Random blood glucose measured at each visit and average glucose recorded by the glucometer were also lower in the NC group vs. the C group (P<0.005). There was a negative correlation between HbA1c and SBGM frequency, and HbA1c in patients testing at least twice a day was lower than in those testing less than twice a day (8.8 +/- 0.2% vs. 9.6 +/- 0.2%, P<0.001). CONCLUSIONS: In this prospective study, having easy access to glucometer strips provided free of charge to patients increased SBGM frequency. The relationship between HbA1c and SBGM frequency supports the view that SBGM is an essential tool in diabetes management.