Unintended Consequences in Use of Increased Risk Donor Kidneys in the New Kidney Allocation Era.

BACKGROUND: The new kidney allocation system (KAS) intends to allocate the top 20% of kidneys to younger recipients with longer life expectancy. We hypothesized that the new KAS would lead to greater allocation of Public Health Service (PHS) increased-risk donor organs to younger recipients. METHODS: Analyses of the Organ Procurement and Transplantation Network data of patients who underwent primary deceased kidney transplantation were performed in pre- and post-KAS periods. RESULTS: The allocation of PHS increased-risk kidney allografts in various age groups changed significantly after implementation of the new KAS, with an increased proportion of younger individuals receiving increased-risk kidneys (7% vs 10% in age group 20-29 y and 13% vs 18% in age group 30-39 y before and after KAS, respectively; P < .0001). This trend was reversed in recipients 50-59 years old, with 31% in the pre-KAS period compared with 26% after KAS (P < .0001). CONCLUSIONS: The new KAS resulted in a substantial increase in allocation of PHS increased-risk kidneys to candidates in younger age groups. Because increased-risk kidneys are generally underutilized, future efforts to optimize the utilization of these organs should target younger recipients and their providers.

Coloduodenovesical Fistula After Simultaneous Pancreas-Kidney Transplant: Case Report and Review of the Literature.

BACKGROUND: Complicated diverticulitis after transplantation occurs in as many as 3.5% of cases and carries a 25% mortality rate. Diagnosis of complicated diverticulitis in this population can be challenging because of abnormal presentations caused by immunosuppression. Only 4 cases of fistulization after kidney transplantation are described in the literature; none occurred after simultaneous pancreas-kidney transplant. METHODS: We present a first case of a coloduodenovesical fistula in a patient 9 years after simultaneous pancreas-kidney transplant. The patient presented with intermittent episodes of elevated creatinine and recurrent urinary tract infection. The presence of fistula was strongly suspected in cystoscopy, but, despite extensive investigation, a fistula tract could not be identified. RESULTS: The patient ultimately underwent surgical exploration for positive cystoscopy examination, continuation of urinary complaints, and presence of multiple colonic diverticula in computed tomography scan. At surgical exploration, a fistula track was identified between the sigmoid colon and duodenal stump of the pancreas allograft. Subsequently, sigmoidectomy, bladder repair, and enteric conversion of the pancreas transplant were performed. CONCLUSIONS: Complications of diverticulitis should be considered in organ transplant recipients presenting with recurrent urinary infection and elevated creatinine, and surgical exploration might be indicated even if unable to well-define the fistula tract.

In vivo estimation of size of experimental tumors.

The precision and accuracy of various estimates of experimental tumor size from lineal dimensions were examined on capsules implanted subcutaneously and inflated to precisely known weights in Fischer 344 rats. The method of tying the final product of three dimensions to the measured excised weight gave a value with no significant systematic bias and the lowest error of estimate (root mean square of deviation = 4.35 g).

Contribution of inert mass to experimental cancer cachexia in rats.

An inert artificial tumor (AFT) was inflated in male F344 rats to simulate, experimentally, the growth in mass of large transplantable tumors that produce cachexia. The AFT depressed host weight gain and skeletal muscle mass up to 30% and food intake up to 20% of the depression induced by tumors of comparable size. When the growth rate of the AFT was low, there was no depression of food intake. Work-induced hypertrophy of skeletal muscles, as assessed by a gastrocnemius tenotomy model, was approximately equal to that of normal, tumor-bearing, and AFT-bearing animals. The AFT elevated host total energy expenditure by 12.5% and compartment-of-energy expenditure attributable to motor activity by 10.5%. The elevation of energy expenditure accounted for most of the depression of weight gain of AFT-bearing animals below that of intact animals. The large mass of most transplantable tumors leads to an overestimate of the malignant tissue-depletive effects of tumor and an under-estimate of the asthenic effects.

Contributions of reduced hunger and premature satiety to cancerous hypophagia in rats.

Tumor-induced reduction in food intake in 2 rat-tumor organisms was distributed approximately equally between reduction in average size (premature satiety) and reduction in frequency (impaired perception of hunger) of effective meals. In both organisms, the frequency of futile meals (activity at food dish without any food ingestion) increased in the tumor-bearing state, and total meal frequency (effective plus futile meals) was unchanged from the tumor-free state. It is proposed that the presence of tumor reduces some meals to zero size and that satiety can occur in the cephalic phase of digestion before any food has been ingested. By this interpretation, cancer hypophagia would be entirely attributable to premature satiety.

Generation and compensation of the cancer cachectic process by spontaneous modification of feeding behavior.

Daily food intake and corresponding feeding activity (measured as duration) and feeding efficiency (amount of food ingested per unit of feeding activity) were measured both in normal Sprague-Dawley and Buffalo rats and during growth of Walker 256 and 4M mammary carcinomas in Sprague-Dawley rats and of Morris 5123 hepatoma in Buffalo rats. Estimates of meal size and frequency were also obtained. Growth of the carcinomas produced a decline in feeding activity accompanied, early in tumor growth, by a compensatory increase in feeding efficiency with no resultant effect on food intake. This compensated decline in feeding activity was due to reduction in average meal duration. Later, meal frequency was also reduced, with further reduction in feeding activity and reduction in food intake. There was little change in average meal size. The hepatoma produced a different detailed pattern of effect on feeding behavior. These effects are not nonspecific reactions to foreign tissue. The effects imply behavioral compensation for the breakdown of a rapidly responding physiological control of food intake and can be interpreted in terms of successive impairment of feeding control mechanisms that have different response rates and different behavioral modes.

Origins of nutritional imbalance in cancer.

Some parallels and differences are considered between the nutritional circumstances that favor carcinogenesis and those that favor tumor growth and host cachexia. From evidence on deletion of physiological feeding controls and changes in feeding behavior during tumor growth and from evidence on differences in sets of available feeding controls and in feeding behavior among normal individuals, it is suggested that acquisition of possibly carcinogenic dietary habits may originate, in part, from innate deficits in physiological feeding controls.

Feeding response of tumor-bearing rats to insulin and insulin withdrawal and the contribution of autonomous tumor drain to cachectic depletion.

The Walker 256 carcinosarcoma growing in Sprague-Dawley rats and the Morris 5123 hepatoma growing in Buffalo rats both produce cachexia but have widely differing patterns of host metabolism and tumor growth. Both organisms respond to exogenous insulin with increased food intake and rate of weight gain of host. The insulin treatment response of food intake was 1.5 to 2 times and of body weight gain was 2 to 3 times that of tumor-free controls. Insulin does not accelerate tumor growth. On withdrawal of insulin, the reactive hypophagia seen in tumor-free rats does not occur in tumor bearers, and the host weight does not return to the expected untreated value as it does in tumor-free rats. Most of the weight gained during insulin treatment of tumor bearers above that gained by tumor-free rats is retained after withdrawal of insulin. A computer model based on the inference from these results, that the tumor-bearing host is blind to body weight error, indicates that this abnormality of feeding control could account for only about one-third of the observed depression of host weight and food intake.

Impairment of feeding response to cold exposure of rats bearing Walker 256 carcinosarcoma.

The feeding response to cold exposure of male Sprague-Dawley rats bearing Walker 256 carcinosarcoma has been measured at 5 degrees, 13 degrees, and 17 degrees exposure. The cold-specific feeding response of the host is estimated taking account of the food cost of the tumor and of changes in food intake induced by weight change of host produced by both cold exposure and tumor growth. The cold-specific feeding response to cold exposure is depressed by about 30% by presence of tumor but is only marginally influenced by tumor size. This tumor-induced impairment of feeding response contrasts with the eventual total abolition and tumor size dependency of feeding response of tumour bearers to caloric density of food.

Extrahypothalamic mediation of changes in feeding behavior induced by growth of Walker 256 carcinosarcoma in rats.

Feeding efficiency (amount of food ingested per unit of feeding activity) was chronically depressed in male Sprague-Dawley rats recovered from the acute aphagia or hypophagia of lateral hypothalamic damage. The extent of depression varied with the severity of the acute feeding response to hypothalamic damage. Growth of Walker 256 carcinosarcoma in intact rats increased feeding efficiency. Chronic lateral hypothalamic damage did not significantly attenuate tumor-induced increase in feeding efficiency but lowered the initial and maximum efficiency levels. Growth of the tumor-bearing host was depressed by residual lateral hypothalamic damage, but this depression was not related to the severity of the acute feeding response to damage.

Insulin reversal of cancer cachexia in rats.

The anabolic effects of exogenous neutral protamine hagedorn insulin on tumor-bearing (TB) and non-tumor-bearing (NTB) rats were examined. Exogenous insulin (2 units/100 g/day) produced similar hypoglycemia in TB and NTB rats. Food intake and body weight gain were significantly increased by insulin in NTB rats. In TB rats in an early stage of cachexia, insulin increased food intake and host weight (total body weight minus tumor weight). In TB rats with severe cachexia, insulin increased food intake and stabilized host weight when untreated TB controls were not eating and were losing weight. When daily insulin administration was started at an early stage of tumor growth and continued until death, there was again significant enhancement of host weight and food intake. Heart and adrenal weights were significantly reduced in insulin-treated TB animals. Tumor growth was not stimulated by insulin treatment. Survival time was slightly reduced in TB rats treated with long-term insulin. Survival time in TB rats randomized to insulin during late cachectic decline was not different from untreated TB controls. Insulin did not have any measurable effect on energy expenditure or the motor activity compartment of energy expenditure in either TB or NTB rats. Insulin treatment can reverse experimental cancer cachexia. It is a nutritional therapy which preferentially feeds the host over the tumor. As yet, its beneficial effects have not prolonged survival of tumor-bearing animals.

Body composition changes in rats with experimental cancer cachexia: improvement with exogenous insulin.

Exogenous insulin treatment has been shown to improve food intake and host weight of cachectic tumor-bearing (TB) rats, but the composition of the host weight gain has not been quantitated. Sixty-six Fischer 344 rats were randomized to seven groups: early nontumor-bearing (NTB) (n = 10) who underwent compositional analysis (CA) on the day the methylcholanthrene sarcoma was implanted in TB rats; pretreatment-NTB (n = 10) and pretreatment-TB (n = 10) who underwent CA 25 days later when rats began treatment with saline or insulin; and finally saline-treated NTB (n = 9), saline-treated TB (n = 9), insulin-treated NTB (n = 9), and insulin-treated TB (n = 9), who underwent CA following 5 days of treatment with daily saline or neutral protamine hagedorn insulin 2 units/100 g. Body weight and food intake were measured daily. For compositional analysis, the tumor was separated from the host in TB rats and the entire rat in NTB animals was homogenized, lyophilized and analyzed for fat, water, protein, potassium, chloride, and sodium. The tumor was processed in a similar fashion. In response to insulin, NTB rats ate significantly more food, and had an increase in body weight gain. Compositional analysis of insulin-treated NTB rats indicated a slight, but insignificant, increase in body fat and a similar insignificant decrease in body protein. TB rats ate significantly less than NTB rats during the 5-day experimental period, and insulin treatment significantly increased food intake to levels similar to NTB animals. Compositional analysis indicated that the tumor-bearing state resulted in a significant decrease in total host water, protein, fat, potassium, sodium, and chloride. Insulin administration resulted in preservation of host nitrogen, fat, potassium, sodium, and chloride in cachectic tumor-bearing rats. Insulin treatment did not affect tumor dry weight or composition. The results suggest that exogenous insulin, can preserve normal host composition of TB rats during cachectic decline.

Parabiotic transfer of cancer anorexia/cachexia in male rats.

To demonstrate that the anorexia and depletion of cachexia reverses on tumor removal, F344 rats underwent sarcoma resection when their food intake fell to 0 g/day. In survivors of surgery, reversal in food intake was apparent within 3 days postoperatively, followed after 2 days by gain in host weight. To detect whether the transmission of anorexia/cachexia in these tumor-bearing (TB) rats was via the circulation, four groups were studied: single non-tumor bearing (NTB); single TB; parabiotic NTB; and parabiotic TB. The measured blood exchange rate between parabiotic halves was 1.2-1.5%/min. No cachectic effect was detected in either half of the NTB parabionts. There was no evidence of sarcoma metastases in the tumor-free half of the parabiotic TB pair. All the rats associated with the presence of tumor showed cachectic effects but the degree and timing of effect varied among the three conditions, single TB, parabiotic TB half, and parabiotic tumor-free half. In all variables examined (fall in food intake, time of first fall in food intake, host weight loss, elevation of blood urea nitrogen) the severities were always in the same sequence: single TB greater than parabiotic TB half greater than parabiotic tumor-free half greater than NTB. In addition, the TB parabiotic pair had a significantly longer survival time and grew a significantly larger tumor than did the single TB animal. The parabiotic tumor had a slower initial growth rate and a slower deceleration rate than the singlet tumor. These results provide evidence for the humoral mediation of cancer-associated cachexia.

Food insecurity and budgeting among Liberians in the US: how are they related to socio-demographic and pre-resettlement characteristics.

Objectives of this study: (1) Examine food insecurity (FI) prevalence and its relationship with sociodemographic and pre-resettlement characteristics; (2) Investigate differences in amount of money spent on food/month by food security status and socio-demographic characteristics. A pilot study with semi-structured in-home interviews was conducted with Liberian caregivers (n = 33). FI was indicated in 61% of households. FI was higher among women >40, had ≤ high school education and those making ≤$1,000/month. Women arriving in US >15 years of age were more likely to be food insecure. Participants spent an average $109/month on groceries/member. Food insecure women, and those without a car spent more money on food (P < .10). Liberian women in this sample experience high levels of FI upon resettlement. Besides poor economic conditions, pre-resettlement characteristics were associated with food security status. These findings call for future research to understand how preresettlement conditions affect food choices, budgeting and thereby food security status.

Retrospective audit: depressive neurosis.

The charts of 100 patients with a primary diagnosis of depressive neurosis were subjected to retrospective audit using a format adapted from the American Psychiatric Association's Model Criteria Sets. Nineteen of the 33 unjustified variations from the audit criteria involved variations from the 8-28 day length of hospital stay. The author raises the question of whether the lower limit of 8 days is sufficiently flexible to permit hospitalization of acutely suicidal patients who can be discharged to outpatient care in less than 8 days.

Cancer cachexia.

Cancer cachexia is a complex syndrome that includes host tissue wasting, anorexia, asthenia, and abnormal host intermediary metabolism. It is present in approximately 50% of cancer patients during treatment and nearly 100% of treated cancer patients at death. Cachexia has a detrimental impact on cancer therapy. The central problem of cancer cachexia is that energy balance is not maintained, and the host has a relative hypophagia which results in host tissue wasting. The tumor by its nature and obligate growth can continue to consume glucose, amino acids, and lipids at the expense of the host. This produces abnormal host intermediary metabolism including elevated glucose production and recycling, decreased muscle protein synthesis, and increased muscle and fat breakdown. The exact mechanisms of cancer cachexia have been only partially elucidated. The identification of signal molecules like cachectin which mediate these changes may be on the horizon. Nutritional support can reverse some of the derangements seen with cachexia, and there is evidence that functional lean body mass or body cell mass can be restored in some (but not all) patients. However, nutritional support has not yet improved response to chemotherapy or radiation therapy, nor has it improved host tolerance of chemotherapy. It has improved operative mortality and morbidity in cachectic cancer patients undergoing major surgical procedures. Optimum host nutritional support appears to be dependent on high insulin concentrations in both humans and rats. Insulin and exercise may be methods to preserve host lean tissue and feed the host rather than the tumor. Future studies depend on better definition of tumor-bearing host metabolism, altering the relationship between neoplasm and host to preferentially feed the host, and making the neoplasm more susceptible to effective treatment.

Growth and body composition during long-term total parenteral nutrition in the rat.

Detailed metabolic data indicating the adequacy of long-term total parenteral nutrition in the rat are not available. In this study an aseptic catheterization technique and a presumed adequate intravenous diet were used to support the nutrition of growing male Fischer 344 rats for a 21-day period. These animals were compared with sham-operated rats after 21 days of ad libitum access to one of two adequate oral diets. Total parenteral nutrition rats demonstrated weight gains that were similar to those in the rats consuming the oral diets. Body composition and nitrogen storage studies indicated fat and protein accumulation in total parenteral nutrition rats that were similar to those in the orally fed animals, but with a tendency toward increased fat and decreased nitrogen retention. These data indicate that apparently normal growth and development can be achieved with total parenteral nutrition in rats by meticulous attention to detail.

Endurance exercise modifies cachexia of tumor growth in rats.

Food intakes, body composition, skeletal muscle mass, muscle protein synthesis, and myofibrillar protein degradation were studied in normal, food-restricted (FR), and Walker 256 tumor-bearing (TB) male Sprague-Dawley rats which were exercised (E) or maintained in a sedentary state. Exercise was enforced 3 times per wk for 100 min X session-1 at 20 m X min-1 on a 13% incline for 7 wk. Tumors were transplanted 3 wk after beginning the exercise program and were allowed to grow for 29 d. Food restriction was initiated during the last 2 wk of tumor growth. Food intakes and body lipid stores were reduced in all E groups, whereas body nitrogen was reduced only in the TBS animals. All E animals had significantly higher gastrocnemius muscle/body weight ratios than their sedentary counterparts, with the greatest ratio noted for the TBE animals. Muscle protein synthesis, measured by incorporation of [3H]tyrosine into gastrocnemius muscle, was significantly depressed in both FR and TB animals. Muscle protein breakdown, estimated by urinary 3-methylhistidine excretion, was significantly elevated in TB animals and slightly increased in FR animals. The results suggest that tumor presence significantly alters protein turnover to a greater extent than elicited by food restriction alone. Additionally, although exercise may have initially protected the animal by retarding tumor growth and muscle mass depletion, in the end, the energy costs of exercise accelerated the catabolic state.

Drug interactions with psychostimulants.

The psychostimulants methylphenidate, dextroamphetamine, and pemoline are among the most common medications used in child and adolescent psychiatry. Often, these agents are used in combination with other medications. This review summarizes reported drug interactions and assesses both causality and clinical significance. A computerized search was undertaken using MEDLINE (1966 to 1998) to obtain all pertinent reports of adverse events associated with the coadministration of psychostimulants and other drugs. A total of 38 reports involving 25 different drugs from various classes were systematically evaluated along with research studies conducted to specifically assess drug interactions. Methylphenidate appeared to be involved primarily in pharmacokinetic interactions suggestive of cytochrome P450 inhibition while dextroamphetamine and pemoline were more often involved in apparent pharmacodynamic interactions. The published data support the safe use of psychostimulants with most classes of medications with few absolute contraindications.

Energy expenditure and motor activity in rats receiving total parenteral nutrition.

Rats with intravascular catheters connected to infusion systems are frequently used in the investigation of nutritional and metabolic problems. Although the animal is often referred to as "unrestrained," there is no information on the effect of the catheter assembly or total parenteral nutrition (TPN) on total (TEE), activity (AEE), and resting (REE) energy expenditure (TEE = REE + AEE). Male Fischer 344 rats were studied in an analytical respiration calorimeter. Normal unoperated rats, aseptically catheterized orally fed rats from postoperative day 1 to 7, and TPN rats were studied. Orally fed catheterized rats had weight loss, negative nitrogen balance, negative energy balance, elevated REE, and normal AEE during the first 4 postoperative days. Their weight gain, positive nitrogen balance, AEE, and REE were almost identical to those of normal rats over postoperative days 5 through 7. REE and AEE in TPN rats were similar to values in normal rats. These data indicate that catheter operation and TPN cause no abnormality in AEE and REE if adequate time is allowed for recovery from catheter operation and strict attention is given to asepsis.