Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats.

BACKGROUND: Most alcoholics experience periods of voluntary alcohol abstinence or imposed alcohol deprivation followed by a return to alcohol drinking. This study examined whether varenicline (VAR) reduces alcohol intake during a return to drinking after periods of alcohol deprivation in rats selectively bred for high alcohol drinking (the alcohol preferring or "P" rats). METHODS: Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2 h/d. After 4 weeks, rats were deprived of alcohol for 2 weeks, followed by reaccess to alcohol for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were fed either vehicle (VEH) or VAR, in doses of 0.5, 1.0, or 2.0 mg/kg BW, at 1 hour prior to onset of the daily alcohol reaccess period for the first 5 days of each of the 3 alcohol reaccess cycles. RESULTS: Low-dose VAR (0.5 mg/kg BW) reduced alcohol intake during the 5 days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0 mg/kg BW and 2.0 mg/kg BW) reduced alcohol intake during the 5 days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. CONCLUSIONS: The results demonstrate that VAR decreases alcohol intake during multiple cycles of alcohol reaccess following alcohol deprivation in rats and suggests that it may prevent a return to heavy alcohol drinking during a lapse from alcohol abstinence in humans with alcohol use disorder.

A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking.

BACKGROUND: This study examined whether naltrexone (NTX) or varenicline (VAR), alone or in combination, can retard the phenotypic expression of a genetic predisposition toward high alcohol drinking in rats selectively bred for high alcohol intake when drug treatment is initiated prior to, or concomitantly with, the onset of alcohol drinking. METHODS: Alcohol-naïve P rats were treated daily with NTX (15.0 mg/kg BW), VAR (1.0 mg/kg BW), a combination of NTX (15.0 mg/kg BW) + VAR (1.0 mg/kg BW), or vehicle (VEH) for 2 weeks prior to, or concomitantly with, their first opportunity to drink alcohol and throughout 21 days of daily 2-hour alcohol access. Drug treatment was then discontinued for 3 weeks followed by reinstatement of drug treatment for an additional 3 weeks. RESULTS: When P rats were pretreated with drug for 2 weeks prior to onset of alcohol access, only NTX + VAR in combination blocked the acquisition of alcohol drinking in alcohol-naïve P rats. When drug treatment was initiated concomitantly with the first opportunity to drink alcohol, NTX alone, VAR alone, and NTX + VAR blocked the acquisition of alcohol drinking. Following termination of drug treatment, NTX + VAR and VAR alone continued to reduce alcohol drinking but by the end of 3 weeks without drug treatment, alcohol intake in all groups was comparable to that seen in the vehicle-treated group as the expression of a genetic predisposition toward high alcohol drinking emerged in the drug-free P rats. After 3 weeks without drug treatment, reinstatement of NTX + VAR treatment again reduced alcohol intake. CONCLUSIONS: A combination of NTX + VAR, when administered prior to, or concomitantly with, the first opportunity to drink alcohol, blocks the acquisition of alcohol drinking during both initial access to alcohol and during a later period of alcohol access in P rats with a genetic predisposition toward high alcohol intake. The results suggest that NTX + VAR may be effective in curtailing alcohol drinking in individuals at high genetic risk of developing alcoholism.

Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism.

BACKGROUND: This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake. METHODS: Alcohol-experienced P rats that had been drinking alcohol (15% v/v) for 2 h/d for 4 weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0, or 2.0 mg/kg body weight [BW]), NTX alone (10.0, 15.0, or 20.0 mg/kg BW), or VAR + NTX in 1 of 4 dose combinations (0.5 VAR + 10.0 NTX, 0.5 VAR + 15.0 NTX, 1.0 VAR + 10.0 NTX, or 1.0 VAR + 15.0 NTX) at 1 hour prior to alcohol access for 10 consecutive days, and the effects on alcohol intake were assessed. RESULTS: When administered alone, VAR in doses of 0.5 or 1.0 mg/kg BW did not alter alcohol intake but a dose of 2.0 mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0 mg/kg BW did not alter alcohol intake but a dose of 20.0 mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment. CONCLUSIONS: Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients.

BACKGROUND: Body mass index (BMI) at its extremes contributes to morbidity and mortality in the general population. Its influence on morbidity and mortality in patients on hemodialysis is not clearly defined. METHODS: The BMI in 1346 patients attending limited-care hemodialysis units across the state of Mississippi was determined, and its relation to one-year mortality and hospital stay was assessed using the Cox proportional hazard model. RESULTS: Of these patients, 89% were black, and 11% were white. Thirty-eight percent of patients were overweight (BMI > 27.5), and 13% were underweight (BMI < 20). The highest (27.60 +/- 0.29, mean +/- SE) and the lowest (24.54 +/- 0.48) BMI were noted in black females and white males, respectively. BMI, race, hematocrit (Hct), and biochemical markers of better nutrition positively influenced the survival, whereas age, serum globulin, and diabetes had a negative influence. In a Cox multivariate analysis, BMI, age, diabetes, prealbumin, and creatinine, but not race, serum albumin, Hct, or serum globulin, retained significant influence on survival. Compared with the normal weight (BMI between 20 and 27.5), the one-year survival rate was significantly higher in the overweight patients and lower in the underweight patients. With a one-unit increase in BMI over 27.5, the relative risk for dying was reduced by 30% (P < 0.04), and with a one-unit decrease in BMI below 20, the relative risk was increased by 1.6-fold (P < 0.01). Furthermore, underweight patients had significantly lower levels of biochemical markers of nutrition and higher frequency and longer duration of hospital stay. CONCLUSION: Adequate dialysis with special attention to proper nutrition aimed to achieve the high end of normal BMI may help to reduce the high mortality and morbidity in hemodialysis patients.

Evaluation of continuous ambulatory peritoneal dialysis.

This study was undertaken to ascertain whether 19 patients maintained on continuous ambulatory peritoneal dialysis (CAPD) for at least 1 year experienced any deterioration in peritoneal membrane function. Selected serum chemistries and skinfold measurements were also evaluated to determine whether patients dialyzed by CAPD could maintain a normal nutritional status. This study demonstrates that patients maintained on CAPD had stable dialysate protein losses, glucose absorption from the dialysate, and constant urea, creatinine, and sodium removal. When these patients were subdivided by incidence of peritonitis, the group with a lower incidence of peritonitis (one episode every 349 +/- 155 SEM days) showed stable serum protein concentration and improvement in upper arm area whereas the group with a high incidence of peritonitis (one episode every 95 +/- 7 SEM days) showed a reduction in upper arm muscle area. Thus, our data suggest that over a 1-year period, there is no deterioration in peritoneal membrane characteristics and CAPD is effective in maintaining the nutritional status of the patient. However, both membrane function and nutritional status may be impaired by frequent episodes of infection.

Peritonitis in continuous ambulatory peritoneal dialysis patients.

Peritonitis is the most important complication of continuous ambulatory peritoneal dialysis (CAPD). We reviewed our experience with peritonitis over a 2 1/2-year period. Our patients spent 4% of their total time on dialysis in hospital due to peritonitis. Thirty-eight percent of the episodes of peritonitis were treated without hospitalization. We evaluated the dialysate bag change technique as commonly performed with currently available devices (extension tubing and titanium Luerlock Tenckhoff catheter adapter). The aseptic techniques described for dialysis extension tubing changes appear adequate (with no increased incidence of peritonitis demonstrated shortly after an extension tubing set change). Long-term sterility is maintained at the dialysate bag puncture port and at the orifice of the dialysis catheter adapter (no positive cultures from the bag port and orifice of the titanium adapter). Etiologic diagnosis of uremia was not a risk factor predisposing to peritonitis. The incidence of peritonitis was greater among patients with less formal education and lower income. Out data suggest that patients with less formal education and of lower economic status be carefully evaluated before commencing CAPD.

Comparison of home hemodialysis to continuous ambulatory peritoneal dialysis.

We evaluated prospectively various outcome measurements of patients assigned initially to continuous ambulatory peritoneal dialysis (CAPD) and home hemodialysis (HHD) from February 1979 to August 1981 and the causes for failures of the techniques. Morbidity was assessed by time in hospital/time on dialysis. Fifty-six patients were trained for CAPD and 37 for HHD. Those assigned to CAPD experienced an increased frequency of hospitalization (7.5% CAPD, 2.8% HHD, respectively) primarily due to episodes of peritonitis. There was also a higher modality failure rate (43% vs. 16%). However, the groups were not comparable in all respects. For example, the CAPD population included 21 patients with major cardiovascular diseases versus only three in the HHD group. The demographic characteristics of both populations including race, sex, age, income, place of residence, marital status, and education were similar. At the time of this study there is no direct evidence showing that healthy patients otherwise able to perform HHD may be maintained with less morbidity for a prolonged period utilizing CAPD. Therefore, we suggest that HHD is the home method of choice for patients able to proceed with this technique. CAPD may be indicated for patients in whom the period of home dialysis is expected to be relatively short and who would be otherwise unable to carry out home dialysis, for example, patients awaiting transplantation and those unable to be maintained on hemodialysis because of impaired cardiac function. To fully evaluate CAPD as a long-term maintenance therapy, a prospective trial must be performed.

Abdominal hernia in patients undergoing continuous ambulatory peritoneal dialysis.

We found abdominal hernias in 12 of 51 patients trained for continuous ambulatory peritoneal dialysis. Five patients were noted to have abdominal hernias before the start of continuous ambulatory peritoneal dialysis, and the conditions of seven patients were diagnosed during routine clinic visits. Four patients had incarceration. We suggest that a careful search for the presence of a hernia be performed at the initial examination for peritoneal dialysis. Continued monitoring of the patient's condition for the development of a hernia is essential. If a hernia is found, elective repair should be performed.

Trisomy 22 in a 20-year-old female.

Trisomy 22 was confirmed in a 20-year-old ambulatory female. Growth and mental retardation plus various dysmorphic features of this syndrome are described and compared with a previous survey. Several interesting unreported findings such as sexual immaturity and gait are discussed in regard to the 22 trisomy syndrome.