Delta opioid peptide [D-Ala2,D-leu5]enkephalin blocks the long-term loss of dopamine transporters induced by multiple administrations of methamphetamine: involvement of opioid receptors and reactive oxygen species

Delta opioid peptide [D-Ala2,D-leu5]enkephalin (DADLE) can prolong organ preservation and increases myocardial tolerance to ischemia. Our study examined the protective property of DADLE against methamphetamine- (METH) induced dopaminergic terminal damage in the central nervous system. Because the neurotoxicity of METH involves reactive oxygen species, we also examined if DADLE might be an antioxidative agent in vitro. DADLE at 2 and 4 mg/kg (i.p.), given 30 min before each METH administration (5 or 10 mg/kg, i.p., four injections in a day at 2-hr intervals), dose-dependently blocked the METH-induced long-term dopamine transporter loss. The opioid antagonist naltrexone blocked this action of DADLE in both aspects of striata but tends not to affect the effects of DADLE in the nucleus accumbens. DADLE did not alter changes in body temperature induced by METH. The reduction of striatal dopaminergic content and tyrosine hydroxylase activity caused by METH, however, were not blocked by DADLE. In vitro, DADLE was approximately equipotent to glutathione in inhibiting both superoxide anion formation induced by xanthine oxidase and hydroxyl radical formation evoked by ferrous/citrate complex. DADLE was only slightly less potent than glutathione in inhibiting the iron/ascorbate-induced brain lipid peroxidation. These results suggest that DADLE can protect the terminal membranes of dopaminergic neurons against METH-induced insult but not the loss of dopaminergic content and tyrosine hydroxylase activity and that this action of DADLE might involve opioid receptors as well as the sequestration of free radical.     

Conceptus, progesterone, and breed effects on uterine protein secretion in swine

This experiment consisted of the following treatment-breed groups: 1) White crossbred gilts, 2) White crossbred gilts treated with progesterone (200 mg/d in corn oil given on d 2 and 3 after estrus), and 3) Chinese Meishan gilts. Pregnant and nonpregnant gilts (n=3 to 6) from each treatment-breed combination were assigned to be slaughtered on d 10, 11, 12, 13, and 15. At slaughter each uterine horn was flushed with 20 mL of minimal essential medium. Uterine flushings were assayed for total protein, acid phosphatase, uteroferrin, retinol-binding protein, and oxytocin. Uterine flush total protein was increased by progesterone treatment, was unaffected by pregnancy status, and was less in Meishans. Similar patterns were found for retinol binding protein and uteroferrin, except that uteroferrin was greater in pregnant than in nonpregnant gilts. Oxytocin was greater in pregnant than in nonpregnant gilts, was not influenced by progesterone treatment, and was similar in Meishan and in White crossbred gilts. These results indicate that the conceptus does not influence secretion of either total protein or retinol binding protein during pregnancy and that the onset of secretion of these uterine proteins may be controlled by progesterone. The presence of the conceptus is associated with increased uteroferrin and oxytocin production. The decreased secretion of uterine proteins in Meishan gilts may partially explain the slower embryonic development that has been reported for this breed.     

Diagnostic focus on the child with myoclonic seizures in isolation or associated with other types of seizures

Myoclonus may be observed in children with mild or severe epileptic syndromes. Both types are seen at characteristic ages, together with other factors: aetiology, family history, hereditary pattern, effect on psychomotor development and EEG-EMG findings. In children with progressive or degenerative encephalopathies and myoclonus, better known as progressive myoclonic epilepsy, there are also specific clinical data, together with biological and genetic markers which permit identification. The most specific clinical characteristics of each of these clinical pictures are described, as are the complementary tests which permit confirmation of these diagnoses.     

CHILD syndrome with linear eruptions, hypopigmented bands, and verruciform xanthoma

The traditional rhomboid transposition flap has been widely used in reconstructive surgery. The authors have modified the original technique by eliminating the creation of the rhomboid defect and by directly transposing the flap into the original postexcisional defect. These changes allow maximum flexibility in flap design and minimize normal tissue loss. The authors retrospectively reviewed the charts of patients who underwent periocular reconstruction with flaps from 1990 through 1995. The authors selected those patients in whom the modified rhomboid flap was used. Functional and cosmetic results and complications were reviewed. Two hundred thirty-two patients were identified in whom 242 flaps were performed. The modified rhomboid flap was used in 101 patients (41.7%). Complications occurred in 23 patients (23%), 19 of whom (19%) were treated medically and four of whom (4%) required an additional surgical procedure. Cosmetic and functional results were classified as very good or excellent in 96 patients (96%). The use of a modified rhomboid flap in the reconstruction of the periocular area offers ample versatility in flap design and minimal normal tissue loss. Functional and cosmetic results are satisfactory in the vast majority of cases.     

La?nnec, re-inventor of the stethoscope?

According to our common medical culture, some facts are simply unquestionable, for instance La?nnec invented the stethoscope. But was he the first one? On a recent trip to Egypt we visited the temple of Kom Ombo, built prior to the roman period and renowned as a medical care center. Today, the tourist is fascinated by the magnificent hieroglyphics on the well-preserved walls testifying to significant advances in various fields of medicine including ophthalmology and gynecology. We were particularly interested by the basreliefs presenting vivid drawings of some of the first medical instruments. We easily identified curettes, scissors, a balance, forceps for dental extraction, and a surgical saw, but were captivated by two other instruments. The first one looked a lot like what La?nnec invented around 1820. The second one was amazingly similar to the instrument we use everyday, with a distal opening and flexible tubes (woven papyrus?) leading to proximal ear pieces. Our Egyptian guide was formal: the stethoscope was invented in Egypt. The scientific impact of our observations leaves something to be desired, but did make us think about the huge gap between the advancement of medical knowledge in ancient Egypt and La?nnec's (re)-invention. Exposed to a similar gap in history, what would our documents stored on CD and video tapes have to say to future touring doctors?     

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.     

Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial

We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara-C). Treatment with 100 nM ara-C for 48h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on the HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and recovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desferioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that desferioxamine strongly potentiated the effects of ara-C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara-C and an iron chelator in terms of antileukaemic effects.     

MRI and articular cartilage

There are considerable laboratory data and information from animal and continuous culture in vitro models to support continuous infusion therapy for penicillins and cephalosporins, but, as yet, the only existing clinical data relate to cephalosporins. Penicillins do not exert concentration-dependent killing in the therapeutic range but have a post-antibiotic effect (PAE) against Gram-positive cocci but not Gram-negative rods. Animal models indicate the time (T) during which the serum concentrations exceed the minimum inhibitory concentration (MIC) of the pathogen [T > MIC] determines outcomes. Pharmacokinetic studies in humans indicate that continuous infusion with penicillins is possible but there are no clinical data on efficacy. Cephalosporins have similar pharmacodynamic properties to penicillins; T > MIC determines outcome. Data related to ceftazidime indicate that the drug concentration at steady-state (Css) should exceed the pathogen MIC by > 1-fold and perhaps by 4- to 5-fold or more. Human pharmacokinetics of ceftazidime administered by continuous infusion to a wide variety of patient groups indicates that Css of > 20 mg/L can easily be achieved using conventional daily doses. Clinical data indicate increased effectiveness of a continuous regimen in neutropenic patients with Gram-negative infection. Furthermore cefuroxime administration by continuous infusion has resulted in lower doses and shorter course durations. Little is known of the pharmacodynamics of monobactams and there are few clinical data on continuous infusion therapy. Carbapenems have different pharmacodynamics to other beta-lactams as they have concentration-dependent killing and a PAE with both Gram-positive and Gram-negative bacteria. While T > MIC has a role in determining outcomes, the proportion of the dosing interval for which serum drug concentrations should exceed the pathogen MIC is less than for other beta-lactams. In vitro models have shown that continuous infusion is effective, as is less frequent dosing. There are few data on continuous infusion of carbapenems but some patients have been treated with once-daily dosing. Clinically, continuous infusion therapy with penicillins and cephalosporins should be considered in patients infected with susceptible Gram-negative rods not responding to conventional therapy. As an approximation, the same total daily dose should be given but a bolus intravenous injection should be give at the start of continuous infusion to ensure Css is reached rapidly. The Css may be difficult to predict and determination of serum drug concentrations may be indicated. Ideally, the Css should be calculated based on the MIC of the potential pathogen and may be higher or lower than the Css achieved by a conventional daily dose.     

Creutzfeldt-Jakob disease: neurophysiologic visual impairments

OBJECTIVE: The predictive value of electrophysiologic visual testing in Creutzfeldt-Jakob disease (CJD) was investigated, and the retinal pathologic findings in three cases are reported. BACKGROUND: The fatal prognosis of CJD, its transmissibility, and the lack of treatment make early diagnosis essential in averting human-to-human transmission. Electroretinogram and visual evoked potentials have been studied in few cases of CJD. METHODS: A visual electrophysiologic examination was performed in 41 consecutive patients referred with suspected CJD. The disease had been diagnosed in 24 patients (CJD group; 15 were confirmed neuropathologically and 9 by clinicolaboratory methods in accordance with diagnostic criteria). The remaining 17 patients were diagnosed with other neurologic disorders, and served as a control group. RESULTS: Flash electroretinogram revealed a significant decrease in the amplitude of the B1 wave (<60 microV) and the B/A ratio (<2) in the CJD group compared with those in the control group. Flash visual evoked potentials revealed no significant difference in latency, but amplitude was increased (>10 microV) in the CJD group, especially in patients with myoclonus. CONCLUSIONS: The visual electrophysiologic abnormalities provide an interesting noninvasive diagnostic tool in idiopathic CJD. The B1-wave decrease is closely correlated with the outer plexiform layer abnormalities observed on neuropathologic examination.