Gradual Withdrawal Research Articles

Long‐Term Ethanol Exposure Alters the Sialylation Index of Plasma Apolipoprotein J (Apo J) in Rats

We have previously shown that chronic ethanol treatment impairs the glycosylation of proteins in the rat liver. Changes in the microheterogeneity of transferrin, a N-sialoprotein under chronic alcohol consumption are well established. Apolipoprotein J, another N-glycoprotein, is a normal component of plasma high-density lipoproteins in the rat and human. Apo J is also highly sialylated and, thus, may be vulnerable to the deleterious actions of ethanol. Therefore, to understand the specific nature of alterations of Apo J sialylation as a consequence of chronic ethanol treatment, we have determined: (1) the sialylation index of Apo J (moles sialic acid per mole Apo J protein) in rats administered ethanol for 4, 6, and 8 weeks and a gradual withdrawal and a follow-up abstinence for 1, 2, and 4 weeks; and (2) enzymatic activities of hepatic sialyltransferase and plasma sialidase during the same periods of alcohol treatment and abstinence in rats. Although no significant differences in the Apo J sialylation index between rats of the control and ethanol groups were found at the 4th week of alcohol treatment, a highly significant loss of 24% (p < 0.001) and 44% (p < 0.001) was found after 6 and 8 weeks, respectively, of alcohol feeding of these animals. Furthermore, a significant recovery of 38% (p < 0.001), 78% (p < 0.001), 84% (p < 0.001) and 96% (p < 0.001) in the sialylation index of Apo J were found, respectively, during withdrawal and 1, 2, and 4 weeks of subsequent alcohol abstinence in these animals. These changes in the sialic acid content of Apo J were accompanied by a similar pattern of changes in the enzyme activities of hepatic sialyltransferase and plasma sialidase in animals undergoing chronic ethanol treatment, withdrawal, and abstinence periods. The analysis of the sialylation index of Apo J seems to be a simple and feasible method to use to evaluate the extent of ethanol exposure.

Tracheo-Innominate Artery Fistula After Tracheostomy

Tracheo-Innominate Artery Fistula After Tracheostomy

Long-Term Ethanol Exposure Alters the Sialylation Index of Plasma Apolipoprotein J (Apo J) in Rats

We have previously shown that chronic ethanol treatment impairs the glycosylation of proteins in the rat liver. Changes in the microheterogeneity of transferrin, a N-sialoprotein under chronic alcohol consumption are well established. Apolipoprotein J, another N-glycoprotein, is a normal component of plasma high-density lipoproteins in the rat and human. Apo J is also highly sialylated and, thus, may be vulnerable to the deleterious actions of ethanol. Therefore, to understand the specific nature of alterations of Apo J sialylation as a consequence of chronic ethanol treatment, we have determined: (1) the sialylation index of Apo J (moles sialic acid per mole Apo J protein) in rats administered ethanol for 4, 6, and 8 weeks and a gradual withdrawal and a follow-up abstinence for 1, 2, and 4 weeks; and (2) enzymatic activities of hepatic sialyltransferase and plasma sialidase during the same periods of alcohol treatment and abstinence in rats. Although no significant differences in the Apo J sialylation index between rats of the control and ethanol groups were found at the 4th week of alcohol treatment, a highly significant loss of 24% (p < 0.001) and 44% (p < 0.001) was found after 6 and 8 weeks, respectively, of alcohol feeding of these animals. Furthermore, a significant recovery of 38% (p < 0.001), 78% (p < 0.001), 84% (p < 0.001) and 96% (p < 0.001) in the sialylation index of Apo J were found, respectively, during withdrawal and 1, 2, and 4 weeks of subsequent alcohol abstinence in these animals. These changes in the sialic acid content of Apo J were accompanied by a similar pattern of changes in the enzyme activities of hepatic sialyltransferase and plasma sialidase in animals undergoing chronic ethanol treatment, withdrawal, and abstinence periods. The analysis of the sialylation index of Apo J seems to be a simple and feasible method to use to evaluate the extent of ethanol exposure.

Use of zolpidem 10 mg as a benzodiazepine substitute in 84 patients with insomnia

The antagonistic effects of zolpidem 10 mg on withdrawal symptoms caused by abrupt or gradual discontinuation (half-dose over 4 nights) of triazolam 0·25 mg in patients with chronic insomnia, who had been receiving regular treatment for over one month, were assessed in a randomized, double-blind, placebo-controlled clinical trial in general practice. Eighty-four patients were enrolled, mostly women (67·9%), with a mean age of 54·3±11·0 years. Twenty-one different general practitioners were solicitated for the recruitment. The subjects were randomized into four groups, and all received triazolam 0·25 mg during the run-in phase from day 1 (D1) to day 3 (D3). The following treatments were given from D4 to D7: triazolam 0·125 mg+zolpidem 10 mg (Group 1); zolpidem 10 mg (Group 2); placebo (Group 3); or triazolam 0·125 mg+placebo (Group 4). Groups 1 and 2 received zolpidem 10 mg from D7 to D24, while Groups 3 and 4 received placebo. Finally, all four groups received placebo (blind withdrawal phase) from D25 to D28. The following assessment criteria were used: clinical global impression (CGI) scale completed by the practitioner; patient questionnaire based on routine sleep criteria, wakefulness and daytime alertness. Secondary criteria were sleep diaries and visual analogue scales. Study drop-outs were reported and explained. The effectiveness/tolerance ratio was found to be statistically significant using the CGI (p<0·007) in favour of zolpidem 10 mg. There was no significant difference in patients subjective assessment between the groups except for nightmares (p<0·04) less frequent in patients receiving zolpidem. Zolpidem was found to be more effective than placebo at D21 (CGI) according to sleep diaries; the zolpidem group showed a statistically significant difference as compared to the three other concerning four sleep parameters: number of awakenings, anxiety, sleep duration, energy. Drop-out rates were significantly lower in the zolpidem group than in other ones (p<0·01). Abrupt and gradual triazolam withdrawal over 4 nights induced withdrawal symptoms. Equally no specific phenomena were observed at the end of the trial during the blind withdrawal phase. This study shows that zolpidem 10 mg improves sleep quality and reduces withdrawal symptoms after abrupt or gradual discontinuation of triazolam 0·25 mg in chronic patients with chronic insomnia. Copyright © 1998 John Wiley & Sons, Ltd.

Role of paraventricular nucleus parvicellular neurons in the compensatory responses to graded hemorrhage.

The goal of this study was to determine the role of the parvicellular component of the paraventricular hypothalamic nucleus (PVH) in the compensatory responses to blood loss. Male Sprague-Dawley rats were prepared with bilateral ibotenate lesions of the parvicellular PVH (PVHx; n = 5) or with sham lesions (Sham; n = 8). After >10 days recovery, hemorrhage was performed by gradual withdrawal of 16 ml/kg blood over 34 min via an indwelling femoral arterial catheter while the rats were conscious and unrestrained. Basal serum corticosterone levels, plasma renin concentration (PRC), mean arterial pressure, and heart rate did not differ between PVHx and Sham, whereas basal hematocrit was lower in PVHx than Sham (40 +/- 1 vs. 44 +/- 1; P < 0.05). After hemorrhage, corticosterone increased fourfold in Sham (P < 0.001) but did not increase significantly in PVHx. However, the blood pressure, heart rate, PRC, and hemodilution responses to hemorrhage were the same in Sham and PVHx during both the normotensive (7-13 ml/kg blood loss) and hypotensive (16 ml/kg blood loss) phases. In conclusion, the parvicellular PVH is essential for the corticosterone response, but not for the cardiovascular or renin responses to blood loss.

The “Picnic” model for research training at African universities: Evaluation and preliminary comparison

What distinguishes the “Picnic” model for research training at African universities from more classical models is reviewed and it is shown how the “Picnic” model deals with remaining drawbacks from the now popular “Sandwich” model. Starting with managerial experiences, criteria guiding this evaluation are used as sub-headings: realistic planning; adequate resource provision; partnership instead of aid; long term impact; high quality supervision; quality and quantity of student input; open and interactive communication; willingness to adapt to local circumstances; ongoing critical reflection; gradual expatriate withdrawal. The training output of the “Picnic” model tests in the four TTMI-countries is assessed after the actual and prospective jobs of its former students. The on-farm quantification of protecting systems/structures led in many TTMI PhD-research cases to improved design criteria for such systems/structures, with direct increases of yield or its preservation. In comparison with the “Sandwich” model, the “Picnic” model particularly incorporates institutional strengthening in the aim that the southern countries will become able to provide adequate education at the postgraduate level, teaching their students how to apply knowledge in their own environment. Degrees obtained at southern universities, therefore, have distinct advantages but joint responsibilities of universities for such degrees are difficult to organize, given the presently existing modes of output-related financing of Dutch universities. In a situation of institutional deterioration, such as Africa is experiencing, the best hope probably lies in strengthening networks of individuals and a collective sense of academic commitment, pending the revival of universities themselves. Emergency research related to the protection of the African agricultural environment by African universities, training NARS staff, must in the long run contribute to restoring an agricultural basis for part of the economies of the many poor African countries. Knowledge developed locally remains the most powerful vehicle for change from within.

Outlay Rates and the Politics of Capital versus Operating Subsidies in Federal Transit Finance

“Outlay rate” is a measure of the lapsed time between the obligation of federal funds for some purpose and the actual drawdown, or expenditure, of those funds. Outlay rates are an important, though often unspoken, reason for the gradual withdrawal of federal operating support of public transit. Rationales for reducing and/or eliminating federal support of transit operations are examined, overall capital and operating outlay rates for a sample of transit operators in California are measured, and possible causes and effects of federal grant outlay rates are discussed. On average, transit operators do, in fact, expend operating grants more quickly than capital grants. However, the overall size of the grant is actually a better predictor of slow outlays than grant purpose. Although the revenues generated by unexpended transit grants represent real revenues to the treasury, the goal of the federal transit program clearly is not simply to maximize such revenues. Evidence from other studies suggests that strict separation of capital and operating grants contributes to less efficient, overcapitalized transit systems, and an emphasis on capital grants may cost the federal treasury in the form of reduced tax revenues resulting from the lower economic multiplier of capital versus operating grants. Thus, it is unlikely that society benefits from a “float-driven” federal transit subsidy policy. Because federal transit grants seek to generate an array of social and economic benefits far broader than interest earned from the float from unexpended grants, the costs of the current capital-oriented or possible capital-only programs should be more systematically considered.

Changed systemic and cerebral hemodynamics and oxygen supply due to gradual hemorrhagic hypotension induced by an external PID-controller in newborn swine

An experimental design including an external closed-loop PID-(proportional-integral-differential-)controller is presented which enables the induction of gradual hemorrhagic hypotension at different stages of blood flow reduction up to stages of critically disturbed systemic and regional hemodynamics and oxygen supply. For this purpose nine newborn piglets (12-26 hours old, body weight 1626+/-160 g) were anesthetized and artificially ventilated. Gradual hemorrhagic hypotension was induced at four different steady state stages (stage 1 = 60 mmHg; stage 2 = 50 mmHg; stage 3 = 40 mmHg; stage 4 = 35 mmHg) every 30 minutes by gradual blood withdrawal using external PID controller equipment. Cardiac output and brain regional blood flows were measured by the colored microsphere technique. Systemic and brain regional hemodynamics and O2 supply, metabolic parameters and blood catecholamine concentrations were obtained under baseline conditions and at every 25th minute of the four different steady state stages. About 35 percent of the calculated total blood volume (cTBV) was withdrawn in order to reach the first stage of hemorrhagic hypotension. Further blood withdrawal of about 10 percent of the cTBV, about 5 percent of the cTBV, and about 3 percent of the cTBV were necessary to reach the other respective hypotensive stages. Gradual hemorrhagic hypotension led to an increasing reduction of the cardiac output at every hypotensive stage up to about 20 percent of the baseline value (p<0.05). This was accompanied by a concomitant increase of the total peripheral resistance to about 2.5 fold (p<0.05) and a huge increase in the blood catecholamine concentrations (epinephrine: about 64 fold; norepinephrine: about 35 fold). The induced redistribution of the circulating blood volume was shunted to the vital organs. Therefore, brain cortical blood flow was slightly increased at stage 1 and stage 2. A significant reduction of rCBF did not occur until stage 4 (p<0.05). Regional cerebrovascular resistance was concomitantly reduced at stage 1 and stage 2 (p<0.05) and thereafter again slightly elevated. Brain cortical oxygen consumption was maintained up to stage 2, reduced by about 20% at the next stage of hemorrhagic hypotension (p<0.05) and reached the lowest level of about 50% from baseline at stage 4 (p<0.05). Excellent accuracy and stability was shown at each stage for the external PID controller equipment, so that each given setpoint of the instantaneous mean arterial blood pressure was reached and stabilized even at the lowest hypotensive stage (stage 1: 59.53+/-0.23; stage 2: 50.03+/-0.56; stage 3: 39.18+/-1.75; stage 4: 35.28+/-0.45 mmHg (mean+/-SD)). We conclude that the experimental design presented, with an external PID controller to induce gradual hemorrhagic hypotension in newborn piglets is sufficient for producing functional states with changed systemic and cerebral features with high stability and accuracy, enabling a systematic study of disturbed regional hemodynamics and energy metabolism under steady state conditions even under critically changed states of the systemic cardiovascular regulation.

The futures of democracy in Pakistan: A liberal perspective

Due to the domination of state institutions over political institutions, Pakistan has not experienced a steady consolidation of democracy over its fifty year history. This is manifest in the lack of roots of constitutionalism, the absence of fully autonomous judiciary, a well developed party system and regularly held fair elections. Recent political developments such as the gradual withdrawal of state institutions particularly the military from the political arena, greater assertiveness of the judiciary, parliaments' curtailment of president powers and rising political consciousness among the people have brightened the chances of survival of democracy in the country. Its further consolidation will depend on the capacity of elected leaders to address the serious problems of ethnic and religious dissensions, financial vulnerability, heavy indebtedness, skyrocketing inflation and serious economic disparities.

P.2.049 A double-blind, placebo-controlled study on gradual withdrawal of antiparkinsonian medication in Chinese schizophrenic patients

In trying to more broadly define outcome in the efficient long-term treatment of patients with schizophrenia it is necessary to consider not only a reduction in psychopathological symptoms but also a successful psychosocial reintegration. Thus, a more exact assessment of psychosocial functioning is needed. Since the GAF (Global Assessment of Functioning) scale and the SOFAS (Social and Occupational Functioning Assessment Scale) are less operationalized and confuse psychosocial facts with psychopathological symptoms, the Personal and Social Performance (PSP) scale was developed [Morosini, P.L., Magliano, L., Brambilla, L., Ugolini, S., Pioli, R. (2000). Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatrica Scandinavica, 1001, 323–329.] containing the four main areas “socially useful activities, personal and social relationships, self-care, as well as disturbing and aggressive behaviour”. Validation of the PSP scale was conducted in a sample of 62 patients with acute schizophrenia. Rating instruments were PSP, GAF, SOFAS, PANSS, CGI, and Mini-ICF-P (Mini-ICF-Rating for Mental Disorders). The results showed good reliability with alpha = .64–.84, high test–retest reliability as well as good inter-rater reliability for the PSP scale. Furthermore, PSP proved good validity with high correlations to GAF (r = .91), SOFAS (r = .91), and Mini-ICF-P (r = − .69). The hypothesis that more critically ill patients would show lower scores on PSP than lesser ill patients was only confirmed for PANSS negative symptoms. Thus, the findings prove the PSP scale to be a reliable and valid instrument for assessing social functioning of patients with schizophrenia during the course of treatment as well as in the acute state.

Airway troubles related to the double-lumen endobronchial tube in thoracic surgery.

Several case reports indicate critical respiratory complications in relation to the double-lumen endobronchial tube (DLT). A prospective survey for the airway problems in using the DLT is presented. One hundred adult patients undergoing thoracotomy for lung cancer were investigated. Tube malposition and airway obstruction were searched using a fiber-optic scope. The endobronchial cuff was positioned just below the trachcal carina while the trachea was intubated with a DLT (Rüsch). The distances of displacement, from the tracheal carina to the bronchial cuff, were measured during anesthesia using an epidural catheter, which had marks every 5 mm. The distances for correcting the tube position were measured at both the bronchial cuff and the level of the teethPaO2,PaCO2 andSPO2 were also measured. Malposition (displacement over 5 mm from the correct position) was found in 42 patients, and 40 of them were in a withdrawal direction, occurring at the postural change and during one-lung ventilation, especially during manipulation of the lung hilum. Correcting distances at the level of the teeth were 15.3-3-times longer than those at the bronchial cuff. Airway deformities and gradual withdrawal of the bronchial cuff were found in association with surgical manipulation. Obstruction occurred at the tips of the tracheal tube in four patients and the bronchial tube in six patients, and at the tip of both in two patients. Hypoxemia (PaO2<60 mmHg) occurred in four patients and hypercapnea (PaCO2>60 mm Hg) in two patients. Most of the DLT obstructions were associated with withdrawal malposition. Great attention to DLT displacement and airway deformity is advised.

Patient Perceptions of Psychological and Physiological Withdrawal Symptoms and Positive Factors Associated with Gradual Withdrawal from Methadone Maintenance Treatment: A Prospective Study

Psychological and physiological withdrawal symptoms and some positive factors were studied in 10 methadone maintenance treatment patients during methadone dose reduction. The subjective ratings were made during a period of 10 days around each réduction occasion, 3 days before dose réduction and 7 days after (i.e., within the periods). To permit comparisons of the subjects' ratings between earlier and later stages of the dose réduction process, a division has been made between the first half and the second half of the total réduction occasions (i.e., between the periods). Three of the patients completed the dose reduction, while the others interrupted their withdrawal attempts. The results show that the aggregate psychological symptoms were rated low, but that, as expected, they increased significantly from the first to the second half of the dose reduction. A significant increase of the psychological symptoms also occurred from the days before each réduction to the days after. The aggregate physiological symptoms were rated very low. A significant increase in rated withdrawal intensity is found within the réduction occasions. There were no significant changes with regard to the aggregate positive factors, either within or between the réduction occasions.

Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment.

Abrupt discontinuation of long-term psychotropic medication can be followed by a high risk of early relapse. This study aimed to quantify the relapse risk over time in patients with schizophrenia following discontinuation of maintenance neuroleptic treatment. Data on the timing of relapses in patients with schizophrenia after withdrawal from neuroleptic therapy were located by a computerized literature search, combined with new data, and evaluated by survival analysis. Data were found for 1210 schizophrenic subjects: 1006 (795 inpatients and 211 outpatients) were withdrawn abruptly from oral neuroleptic therapy, and 204 discontinued treatment gradually (> or = 3 weeks) or stopped treatment with depot neuroleptic drugs. After abrupt discontinuation of oral medication, the risk of relapse reached 50% within 30 weeks, with remarkably little additional risk thereafter to 3.7 years; inpatients relapsed more rapidly than did outpatients (10 vs 18 weeks to a 25% relapse risk). In studies including subjects whose drug therapy was withdrawn abruptly (n = 49) vs gradually (n = 58), relapse was earlier after abrupt discontinuation (25% risk in 6 vs 10 weeks), with a persistent difference for at least 6 months. The relapse risk was high within 6 months of discontinuing oral neuroleptic therapy, particularly in hospitalized patients. Most patients who remained stable for 6 months continued to do so for long periods without medication, indicating clinical heterogeneity. Drug-withdrawal stressors, related to long-term pharmacodynamic adaptations, are implicated. Since the risk was lower after gradually discontinuing oral neuroleptic therapy or stopping depot injections, early relapse may be spared by a slow removal of drugs.

Dyskinesias Secondary to Gradual Neuroleptic Drug Withdrawal in Elderly Nursing Home Residents

Dyskinesias Secondary to Gradual Neuroleptic Drug Withdrawal in Elderly Nursing Home Residents

Fertilizer use and maize production in Sub-Saharan Africa

In sub-Saharan Africa, greater use of mineral fertilizers is crucial to increasing food production and slowing the rate of environmental degradation. Regional growth rates in fertilizer consumption have never been particularly high, in part because the real price of fertilizer is higher in Africa than in many other developing regions. As subsidies have been removed and exchange-rate distortions corrected over the past decade or more, relative prices paid by farmers have risen to reflect more closely the economic cost of fertilizer. Consumption growth has thus slowed even more. Nonetheless, during the period of declining growth in consumption, fertilizer use on cereals, particularly maize, has become relatively more important than use on cash crops. Strategies for increasing fertilizer use should thus direct more attention to maize and other important staples. In higher potential areas, some fertilizer use on maize is often economically profitable even at higher relative prices of fertilizer. Additional research on the limiting nutrient under farmers' conditions or on the interactions between nutrients and other crop-management factors could help to increase profitability. Policy analysis for Africa's fertilizer sector has tended to focus on subsidies and to neglect other important issues, such as solving credit problems at many points in the marketing channel, supporting appropriate agricultural research, and developing and maintaining infrastructure. Agricultural sector strategies that give sufficient attention to these issues must be developed. Although subsidy removal must be one ultimate policy objective, we recommend gradual withdrawal in countries where fertilizer consumption levels are relatively high. Because many African governments require time and stability to develop policy capacity, detailed institutional analyses can help design second-best solutions to problems of fertilizer policy.

Drug replacement treatments: is amphetamine substitution a horse of a different colour?

Advocates of amphetamine substitution therapy argue that needle sharing by amphetamine users, and associated infectious disease risk, outweigh the risks associated with oral dexamphetamine substitution prescribing, and that substitution can allow stabilization and gradual withdrawal of patients, or maintenance. Others note that amphetamine users are not generally physically dependent, dexamphetamine prescribing can lead to increased drug use and psychosis, and that there are possible neurotoxic effects from prolonged chronic exposure to amphetamines. Research on the impact of amphetamine and cocaine prescribing on drug use, injecting, social adjustment and criminal involvement is lacking apart from a small number of retrospective case reports. Early experience in the United Kingdom leads to the view that amphetamine maintenance was a therapeutic failure. More recently, clinicians have expressed confidence that the approach has merit, and while their claims should not be discounted there remains no empirical basis to support them. Although dexamphetamine substitution therapy has been heralded as an important intervention to reduce injecting behaviour and associated infectious disease risk, there is very little research which attests to its success in reaching this goal. Indeed, what is known regarding patterns of amphetamine use and the effects of prolonged use of the drug raise serious doubts as to the efficacy of amphetamine maintenance. There is an urgent need for randomized or case-controlled trails of the efficacy of these procedures. Until such empirical comparative research is available, the benefits to be gained from dexamphetamine substitution therapy remain speculative and opinion-based.

Isolation of Human T-Cell Leukemia Virus Type I From a Transformed T-Cell Line Derived Spontaneously From Lymphocytes of a Seronegative Egyptian Patient With Mycosis Fungoides

Mycosis fungoides (MF) is a rare form of cutaneous T-cell lymphoma that may be associated with human T-cell leukemia virus type I (HTLV-I) infection. Using the polymerase chain reaction, the HTLV-I pX region was constantly detected in the genomic DNA extracted from peripheral blood mononuclear cells (PBMCs) of an HTLV-I antibody-seronegative Egyptian MF patient enrolled in a study to isolate HTLV-I from North Africa. A CD4+ and interleukin-2 (IL-2) receptor-positive T-cell line was established when the phytohemagglutinin-stimulated PBMCs of that patient were maintained in IL-2-containing culture medium. The cell line (EMF) was initially IL-2 dependent and then became IL-2 independent after gradual withdrawal of the IL-2. The cells reacted positively with monoclonal antibodies specific for the HTLV-I Env or HTLV-I Gag proteins. Using the Southern blot analysis, HTLV-I provirus could be detected in the genomic DNA extracted from the EMF cells. Limited nucleotide sequence of the env region showed more than 95% homology between the EMF provirus and other known HTLV-I isolates. Western blot analysis of the cell lysates showed the expression of the HTLV-I structural proteins. These data imply that a transforming HTLV-I provirus may be present, at least in certain cases of MF, regardless of the presence or absence of the specific antibodies.

Tidal volume maintenance during weaning with pressure support.

Ventilation was measured in 31 difficult-to-wean patients while pressure support (PS) was reduced by 5 cm H2O every 20 min. Weaning had to be aborted in 14 of 31 patients (Group F) because they met predefined distress criteria. The remaining 17 patients who were able to complete the "weaning test" (Group S) had larger static respiratory compliances (Cstat = 0.08 +/- 0.02 versus 0.05 +/- 0.01 L/cm H2O, p < or = 0.05) and a lower dead space to tidal volume ratio (0.55 +/- 0.05 versus 0.64 +/- 0.06, p < or = 0.05). Group S patients had a larger tidal volume (VT) than did those of Group F at most PS settings. The groups differed with respect to VT maintenance during PS withdrawal (p < 0.01). In Group S, VT fell exponentially with machine support and stabilized at PS levels between 5 and 10 cm H2O. In contrast, Group F patients defended VT at higher PS settings but were unable to maintain VT during distress. Ventilatory response parameters such as the rapid shallow breathing index were of limited value in predicting weaning outcome and yielded receiver operator curve area values between 0.66 and 0.82 over the range of PS settings tested. We conclude that the gradual withdrawal of machine support does not facilitate the recognition of impending respiratory failure.

Outcome of children with opsoclonus-myoclonus regardless of etiology

Within the past 11 years, 11 patients with opsoclonus and myoclonus, with or without a history of neuroblastoma, have been admitted to Children's Memorial Hospital. Eight of the 11 children had an occult neuroblastoma. Eight children have had subsequent delayed development with motor incoordination and speech delay (7 with neuroblastoma, 1 without). Nine of 11 children initially were treated with ACTH, 1 child was treated with prednisone, and 1 was not treated. Nine of the 10 children who were treated had recurrences of symptoms during the gradual withdrawal or discontinuation of ACTH. Often the ACTH had to be restarted or increased, although several times the episodes were self-limited, not requiring treatment after ACTH was withdrawn. We found prednisone was ineffective in controlling opsoclonus-myoclonus regardless of etiology. The majority of children with opsoclonus-myoclonus, regardless of etiology, have developmental delay, more severe and at a higher rate than previously reported. When a neuroblastoma was present, tumor removal did not improve symptoms. Although limited in size, our study indicates patients with opsoclonus-myoclonus without an associated neuroblastoma have a better chance for normal neurologic development ( 2 3 versus 1 8 ).

Planning for Succession

Ownership transition provides for the gradual withdrawal of existing owners; allows a firm to admit new people into ownership; and assures the continuity of operations. This article describes how a firm can ease the transition from one generation of owners to the next. First the current management group must determine who will be eligible for ownership, based on technical competence and skills in areas such as marketing, human resources, project management and collecting accounts receivable. Firms must then establish a step-by-step plan for the ownership transition that addresses issues including external and internal communications regarding the transition, dealing with employees who won’t be offered ownership, financing options for stock purchases among new owners, how to determine the firm’s value, how to conduct the buyout of major stockholders and how to indoctrinate new owners to some of the responsibilities of ownership.