Prevalence of fetal alcohol syndrome in the Top End of the Northern Territory.

OBJECTIVE: To establish the prevalence of fetal alcohol syndrome (FAS) in the Top End of the Northern Territory (NT), Australia, in both the indigenous and non-indigenous populations. Fetal alcohol syndrome is a preventable disease that is a major cause of intellectual handicap worldwide. The prevalence of FAS in the NT, and in Australia as a whole, is unknown. METHODOLOGY: Cases were identified through retrospective review of medical records and outpatient letters of children seen by Royal Darwin Hospital paediatric staff. Cases were also identified by tracing potentially affected siblings, or incidentally during clinical work. All children were born between 1990 and 2000, and lived in the Top End of the NT. RESULTS: Seventeen children were identified with definite FAS. Twenty-six children with partial FAS or alcohol-related neurodevelopmental disorder (ARND) were also identified. The prevalence of FAS in the Top End of the NT was calculated to be 0.68 per 1000 live births. The prevalence might be as high as 1.7 per 1000 live births, if cases identified as partial FAS or ARND because of insufficient records, were assumed to have full FAS. In indigenous children, the corresponding prevalence was calculated to be between 1.87 and 4.7 per 1000 live births. The difference between indigenous and non-indigenous rates of FAS was significant (P < 0.0001). CONCLUSIONS: The prevalence of FAS in indigenous children of the Top End of the NT is comparable to the high rates in indigenous populations worldwide.

Electrical stimulation of abdominal muscles for control of blood pressure and augmentation of cough in a C3/4 level tetraplegic.

OBJECTIVES: Evaluation of a FES (Functional Electrical Stimulation) device for the relief of postural hypertension and augmentation of cough in a C3 ventilator-dependent tetraplegic. STUDY DESIGN: A single case study. SETTING: A supra regional spinal unit in the UK. METHOD: A dual channel stimulator was designed that allowed selection and initiation of two predetermined stimulation intensities using a chin controlled joystick. Two sets of 70 mm diameter electrodes were placed either side of the abdomen. Approximately 80 mA, 300 micros, 40 Hz was required for assisted cough while about 40 mA was required for maintenance of blood pressure. After eating, the lower level stimulus is self-administered every 3 to 5 min gradually increasing the time between groups of burst to once every hour after 90 min. RESULTS: Following eating, a blood pressure of 60/45 mmHg was recorded. After five 1 s bursts of stimulation in quick repetition, this was increased to 133/92 mmHg. After 2 min blood pressure had fallen to 124/86 mmHg and to 93/66 after a further 4 min. The electrical stimulation was then repeated, returning the blood pressure to the previous higher level. Measurement of peak expiratory flow showed an increase from 275 l/min for an unassisted cough to 425 l/min when using the device. CONCLUSION: The device is used every day. The user is now independent in coughing function and no longer requires suction or manual assistance. Maintenance of blood pressure has significantly improved his quality of life.

Limits of detection of regional differences in vasodilated flow in viable myocardium by first-pass magnetic resonance perfusion imaging.

BACKGROUND: Perfusion imaging techniques intended to identify regional limitations in coronary flow reserve in viable myocardium need to identify 2-fold differences in regional flow during coronary vasodilation consistently. This study evaluated the suitability of current first-pass magnetic resonance approaches for evaluating such differences, which are 1 to 2 orders of magnitude less than in myocardial infarction. METHODS AND RESULTS: Graded regional differences in vasodilated flow were produced in chronically instrumented dogs with either left circumflex (LCx) infusion of adenosine or partial LCx occlusion during global coronary vasodilation. First-pass myocardial signal intensity-time curves were obtained after right atrial injection of gadoteridol (0.025 mmol/kg) with an MRI inversion recovery true-FISP sequence. The area under the initial portion of the LCx curve was compared with that of a curve from a remote area of the ventricle. Relative LCx and remote flows were assessed simultaneously with microspheres. The ratio of LCx and remote MRI curve areas and the ratio of LCx and remote microsphere concentrations were highly correlated and linearly related over a 5-fold range of flow differences (y=0.96 x+/-0.07, P<0.0001, r(2)=0.87). The 95% confidence limits for individual MRI measurements were +/-35%. Regional differences of >/=2-fold were consistently apparent in unprocessed MR images. CONCLUSIONS: Clinically relevant regional reductions in vasodilated flow in viable myocardium can be detected with 95% confidence over the range of 1 to 5 times resting flow. This suggests that MRI can identify and quantify limitations in perfusion reserve that are expected to be produced by stenoses of >/=70%.

Assessment of regional differences in myocardial blood flow using T2-weighted 3D BOLD imaging.

The feasibility of detecting regional differences in myocardial blood flow based on the blood oxygen level-dependent (BOLD) effect was evaluated in vivo in dogs (N = 9) using a 3D T2-prepared segmented gradient-echo sequence at 1.5 T. Regional differences in myocardial blood flow were created by administering adenosine through a catheter placed in the left circumflex coronary artery (LCX). The difference in the R2 (1/T2) relaxation rate between the left ventricular myocardial region supplied by the LCX and regions supplied by the left anterior descending coronary artery (LAD) or septal artery during adenosine administration was correlated to the corresponding regional myocardial blood flow difference determined using fluorescent microspheres. A correlation coefficient of 0.80 was found between the MR BOLD measurements and the myocardial flow assessment. Our results show that the sequence used in this study allows fast 3D BOLD imaging of the heart, and is a promising technique for detecting regional myocardial perfusion differences.

Myofibrillar disruption in hypocontractile myocardium showing perfusion-contraction matches and mismatches.

Chronically instrumented dogs underwent 2- or 5-h regional reductions in coronary flow that were followed, respectively, by balanced reductions in myocardial contraction and O(2) consumption ("hibernation") and persistently reduced contraction despite normal myocardial O(2) consumption ("stunning"). Previously unidentified myofibrillar disruption developed during flow reduction in both experimental models and persisted throughout the duration of reperfusion (2-24 h). Aberrant perinuclear aggregates that resembled thick filaments and stained positively with a monoclonal myosin antibody were present in 34 +/- 3.8% (SE) and 68 +/- 5.9% of "hibernating" and "stunned" subendocardial myocytes in areas subjected to flow reduction and in 16 +/- 2.5% and 44 +/- 7.4% of subendocardial myocytes in remote areas of the same ventricles. Areas of myofibrillar disruption also showed glycogen accretion and unusual heterochromatin clumping adjacent to the inner nuclear envelope. The degrees of flow reduction employed were sufficient to reduce regional myofibrillar creatine kinase activity by 25-35%, but troponin I degradation was not evident. The observed changes may reflect an early, possibly reversible, phase of the myofibrillar loss characteristic of hypocontractile myocardium in patients undergoing revascularization.

Immunoexpression of villin in neuroendocrine tumors and its diagnostic implications.

BACKGROUND: Villin, a 95-kd cytoskeletal protein associated with axial microfilament bundles of brush border microvilli, is mostly restricted to intestinal glandular tumors. Villin immunoexpression was recently observed in a small number of carcinoids of the intestinal tract and lung, but its significance in a broad category of neuroendocrine tumors has not been evaluated. DESIGN: A total of 114 neuroendocrine tumors of different origins were tested for villin expression. They included gastrointestinal carcinoids (n = 30), lung carcinoids (n = 15), small cell carcinomas of the lung (n = 24), small cell carcinomas of other sites (n = 15), islet cell tumors (n = 8), Merkel cell carcinomas (n = 6), paragangliomas (n = 6), and others (n = 10). Nine round cell sarcomas were tested as well. RESULTS: Villin immunoreactivity was present in 85% of gastrointestinal carcinoids and small cell carcinomas, but was found in only 40% of lung carcinoids. Other tumors tested were virtually negative for villin. In general, while cytoplasmic reactivity was most common, a characteristic apical membranous pattern simulating brush border was seen in 76% of the gastrointestinal carcinoids and in 50% of the lung carcinoids. CONCLUSIONS: We found that villin was predominantly restricted to gastrointestinal neuroendocrine tumors (excluding islet cell tumors), although a small number of bronchial carcinoids may be positive as well. These results suggest a role for villin in the differential diagnosis of neuroendocrine tumors.

Coronary vascular responsiveness to adenosine is impaired additively by blockade of nitric oxide synthesis and a sulfonylurea.

OBJECTIVES: We sought to define effects of glibenclamide, a sulfonylurea known to block ATP-dependent potassium (KATP) channels, and Nomega-nitro-L-arginine methyl ester (L-NAME), an L-arginine analog known to block nitric oxide (NO) synthesis, on coronary vascular responsiveness to adenosine. BACKGROUND: The role of adenosine in coronary flow regulation becomes increasingly important when KATP channel function or NO synthesis is impaired. Both variables are potentially altered in patients with coronary artery disease taking a sulfonylurea. METHODS: Dose-response curves relating coronary conductance to plasma adenosine concentration were obtained by using intracoronary infusions of adenosine (10 to 1,000 microg/min) in chronically instrumented dogs. RESULTS: ED50, the plasma concentration of adenosine needed to produce 50% of the maximal increase in conductance under baseline conditions, increased threefold after either 1 or 10 mg/kg of L-NAME. ED50 also increased in response to glibenclamide in a dose-related fashion (5.7-fold increase per 1 mg/kg body weight of glibenclamide). Effects of combined blockade of KATP channels and NO synthesis were additive, with increases in ED50 as high as 15-fold. Both L-NAME and glibenclamide increased systemic pressure and reduced coronary conductance, confirming the roles of NO and KATP channels in regulating coronary and systemic vascular tone under rest conditions as well as during stress. CONCLUSIONS: Coronary vascular responsiveness to adenosine is blunted in vivo by both L-NAME and glibenclamide. Effects of the sulfonylurea and blockade of NO synthesis are additive and can limit coronary vasodilation as well as other responses involving KATP channels and NO.

Proportionate reversible decreases in systolic function and myocardial oxygen consumption after modest reductions in coronary flow: hibernation versus stunning.

OBJECTIVES: This study sought to determine whether modest short-term reductions in coronary flow can produce subsequent proportionate reductions in myocardial function and O2 consumption compatible with myocardial hibernation. BACKGROUND: Acute studies indicate that myocardial energy utilization can be downregulated during moderate flow reduction. Whether this apparently beneficial adjustment persists into the reperfusion period is unsettled because most postischemic contractile dysfunction has been presumed to represent stunned or irreversibly injured myocardium. METHODS: Responses of regional myocardial function and O2 consumption were assessed in chronically instrumented dogs after approximately 50% reductions in flow for 2 h (n = 8) or repeated 2-min total coronary occlusions (n = 6). RESULTS: When unrestricted perfusion was restored after sustained partial occlusions, regional function and O2 consumption stabilized at proportionate, systematically decreased levels ([mean +/- SEM] 80 +/- 3.1% and 81 +/- 5.1% of control values, both p < 0.05) and then returned to control values within 24 h. Similar proportionate reductions occurred after as few as five cycles of brief total occlusion (79 +/- 5.1% and 83 +/- 1.6% of control values, both again p < 0.05); these persisted with additional occlusions and then returned to baseline values within 3 h. The absence of irreversible injury was documented histologically in both series. Sham animals (n = 5) showed no changes in regional function or O2 consumption throughout similar experimental periods. CONCLUSIONS: Moderate decreases in coronary flow or repeated brief coronary occlusions can be followed by proportionate reversible reductions in regional systolic function and O2 consumption compatible with the traditional definition of myocardial hibernation. These findings emphasize the complexity of myocardial responses to flow restriction and call attention to limitations in characterizing reversibly hypocontractile myocardium as simply hibernating or stunned.

Blockade of nitric oxide synthesis reduces myocardial oxygen consumption in vivo.

BACKGROUND: Although cardiac myocytes and coronary vascular endothelium are known to express a constitutive form of NO synthase, the in vivo effects of tonic endogenous production of NO on myocardial O2 consumption and contractile performance remain unclear. METHODS AND RESULTS: The effects of blockade of NO synthase were determined in intact dogs. Myocardial O2 consumption decreased systematically over a wide range of hemodynamic demand after the systemic administration of N omega-nitro-L-arginine methyl ester (L-NAME) or N omega-nitro-L-arginine. Decreases after doses of 1 and 10 mg/kg L-NAME averaged 23 +/- 3.8% and 34 +/- 7.2% at a heart rate of 90 bpm in open-chest animals. Similar reductions occurred after the administration of L-NAME and N omega-nitro-L-arginine in chronically instrumented animals and were unaffected by beta-adrenergic blockade. Intracoronary infusion of L-NAME in chronically instrumented animals reduced both myocardial O2 consumption and regional segment shortening, even at a dose that did not increase systemic arterial pressure. CONCLUSIONS: The blockade of NO synthesis reduces myocardial O2 consumption in vivo. The decrease in O2 consumption is accompanied by a decrease in segment shortening. It involves a direct myocardial action of NO, is unaffected by beta-blockade, and is consistent with in vitro studies indicating that low levels of NO augment contractile performance by inhibition of a cGMP-dependent phosphodiesterase.

The effects of goal setting and self-instruction on learning a reading comprehension strategy: a study of students with learning disabilities.

This study examined the contributions of instruction in goal setting and self-instruction, separately and combined, on the acquisition, maintenance, and generalization of a reading comprehension strategy by fourth-through sixth-grade students with learning disabilities. A previously validated strategy involving the use of story structure to analyze and remember story content was taught to 47 students with learning disabilities using the self-regulated strategy development (SRSD) model. Comparisons were made among students with learning disabilities in four conditions (strategy instruction, strategy instruction plus goal setting, strategy instruction plus self-instruction, and strategy instruction plus goal setting and self-instruction). Result indicated that instruction in the reading strategy produced meaningful, lasting, and generalizable effects on students' story comprehension skills. Furthermore, the comprehension performance of the students with learning disabilities after strategy instruction was indistinguishable from that of a social comparison group of normally achieving students. Explicit instruction in goal setting and self-instruction, however, did not augment the comprehension performance of students with learning disabilities.

A comparison between Mohs micrographic surgery and wide surgical excision for the treatment of dermatofibrosarcoma protuberans.

BACKGROUND: There is growing evidence that Mohs micrographic surgery (MMS) is the treatment of choice for dermatofibrosarcoma protuberans (DFSP). OBJECTIVE: This study retrospectively compared the recurrence rates of DFSP after MMS with those after wide surgical excision; results at the Mayo Clinic and in the world literature were evaluated. In addition, preoperative tumor sizes and postoperative defect sizes after MMS were compared to determine whether MMS conserved more normal tissue than wide surgical excision. METHODS: The medical records of 84 patients with DFSP who had been treated at the Mayo Clinic were reviewed. They were categorized into two treatment groups: MMS and surgical excision. RESULTS: Fifteen patients with DFSP who underwent MMS had follow-up data available; one of these patients had local recurrence (recurrence rate, 6.6%; average duration of follow-up, 40 months). Thirty-nine patients had wide excision; four of these patients had local recurrences and one had pulmonary metastases (recurrence rate, 10%; average duration of follow-up, 36 months). A review of the world literature revealed neither local recurrences nor metastases in the 11 studies in which DFSP was treated with MMS. Overall, including our results, the average recurrence rate of DFSP after MMS was 0.6% (range, 0% to 6.6%) and the total recurrence rate was 1.6% (1 of 64). Including our series, DFSP was treated with wide excision in 15 studies; the average recurrence rate was 18% (range, 0% to 60%) and the total recurrence rate was 20% (100 of 489). In eight published studies, DFSP was surgically resected with undefined or conservative excisional margins; the average recurrence rate was 43% (range, 26% to 60%) and the total recurrence rate was 44% (140 of 317). A surgical margin of 2.5 cm to deep fascia was required for complete clearance of all tumors treated with MMS. Twenty-two percent of tumors were removed with a 0.5 cm margin, 50% with a 1.0 cm margin, 67% with a 1.5 cm margin, and 89% with a 2.0 cm margin. CONCLUSION: On the basis of our results and data compiled from the literature, MMS may be the treatment of choice for DFSP because of its high cure rate and maximal conservation of tissue.

Serum C-reactive protein. A useful and economical marker of immune activation in renal transplantation.

This study investigated whether serial daily measurements of serum C-reactive protein (sCRP) in 187 renal allograft recipients could help discriminate episodes of renal dysfunction due to rejection or cyclosporine (CsA) nephrotoxicity and help adjust immunosuppression in the early posttransplant period. Excellent primary graft function was associated with an initial peak of sCRP on day 2 after transplant (median, 29 microg/ml; range, 4 to >200 microg/ml) with a return to <20 microg/ml in all patients by day 5 (median, 7 microg/ml; range, 2-19 microg/ml). Stable graft function (mean creatinine, 155 microg/ml) was accompanied by a median sCRP of 4 microg/ml (range, 1-19 microg/ml). In 30 episodes of rejection responsive to methylprednisolone, sCRP was initially significantly raised to a median of 49 microg/ml (P<0.001) but fell rapidly in response to treatment to a median of 11 microg/ml and continued to fall. In 19 episodes of rejection unresponsive to methylprednisolone, median initial sCRP levels were significantly higher (P<0.001) at 119 microg/ml and were still at a median of 77 microg/ml at the end of the treatment. Twenty-four patients in whom renal dysfunction was associated with CsA nephrotoxicity showed no increase in sCRP concentrations; median sCRP concentrations remained at <5 microg/ml throughout the episodes. A similar pattern was seen in patients with acute tubular necrosis. Serial sCRP measurements provide economical and reproducible evidence of immune activation, help discriminate renal dysfunction due to CsA nephrotoxicity or rejection, and allow appropriate modification of immunosuppressive therapy.

Endothelium-derived relaxing factor (nitric oxide) has a tonic vasodilating action on coronary collateral vessels.

OBJECTIVES: We sought to determine whether endothelium-derived relaxing factor (nitric oxide) exerts a tonic vasodilating effect on coronary collateral channels developed in response to myocardial ischemia. BACKGROUND: Although the coronary collateral circulation is known to react to several vasoactive agents, the role of endogenously produced nitric oxide is unclear. METHODS: Coronary collateral channels were induced in the left circumflex artery bed of 12 chronically instrumented dogs by either ameroid implantation or repeated occlusion of the left circumflex coronary artery. With the native circumflex artery occluded, aortic and circumflex pressures and microsphere flows were measured before and after systemic administration of NG-nitro-L-arginine methyl ester, an arginine analogue known to block the synthesis of nitric oxide. RESULTS: NG-nitro-L-arginine methyl ester increased mean aortic pressure from a mean +/- SEM of 92 +/- 4 to 114 +/- 4 mm Hg, whereas pressure in the occluded circumflex artery decreased from 61 +/- 4 to 55 +/- 4 mm Hg. The increase in aortic-circumflex pressure gradient (from 31 +/- 4 to 59 +/- 5 mm Hg) was accompanied by a decrease in flow in the circumflex bed (from 1.31 to +/- 0.14 to 1.09 +/- 0.15 ml/min per g), resulting in an increase in coronary collateral resistance averaging 173 +/- 37% (from 26 +/- 4 to 64 +/- 9 mm Hg/ml per min per g, p < 0.01). The increase in collateral resistance could be partially reversed by administration of L-arginine. CONCLUSIONS: We conclude that nitric oxide normally exerts a substantial tonic dilating effect in coronary collateral vessels. Disease-induced alterations in endothelial function may limit collateral perfusion importantly.

The spelling for writing list.

Four different vocabulary lists based on the study of children's writing were used to generate a basic spelling list for students with learning disabilities and other poor spellers. For each vocabulary list, the smallest number of different words that accounted for 80% of the words children used in their writing were identified. Words that were common to only one or two of the lists or not normally used by children until fourth grade or later were eliminated. Each word was assigned a grade placement based on difficulty, pattern of occurrence in children's writing, and placement on current vocabulary lists and spelling materials. The resulting spelling list of 335 words is provided.

Lack of correlation between IgG T-lymphocyte flow cytometric crossmatches with primary renal allograft outcome.

The flow cytometric crossmatch (FCXM) has been reported to be more sensitive and capable of detecting very low levels of antibodies than the normally used complement dependent cytotoxicity test. We studied both the two colour IgG T cell FCXM and CDC-XM in 146 renal allograft recipients, 111 primary and 35 regrafts, of which 26% (29/111) of 1st and 20% (7/35) of regrafts had a positive FCXM. There was no overall correlation between the FCXM results and early graft outcome in primary renal allografts. The FCXM did not appear to have any advantage over the CDC-XM in predicting graft outcome in unsensitized first grafts. In the small number of regrafts studied, a positive FCXM was associated with a higher degree of graft failure. FCXM can exhibit false negative results if sera are used solely neat although these prozone phenomena do not influence subsequent graft outcome.

Improving learning disabled students' skills at composing essays: self-instructional strategy training.

This study was conducted to determine if self-instructional strategy training would improve learning disabled students' writing. Students were taught a strategy designed to facilitate the generation, framing, and planning of argumentative essays. Training effects were investigated using a multiple-baseline across-subjects design, with multiple probes in baseline. Strategy instruction had a positive effect on students' writing performance and self-efficacy. Effects were maintained over time and transferred to a new setting and teacher. Evidence for generalization to a second genre, story writing, was also obtained. The students and their special education teacher recommended the use of the strategy with other students.