Effects of Acute and Chronic Inflammation on the Pharmacokinetics of Prednisolone in Rats

The effects of acute and chronic stages of carrageenan-induced air-pouch inflammation on the pharmacokinetics of prednisolone were studied in male Wistar rats. Chronic inflammation produced a significant increase in the area under the curve (AUC) of prednisolone compared to control animals (6594 ± 2144 vs 3530 ± 2164 µg · hr/ L). The effect of acute inflammation was not significant (AUC = 4996 ± 3813). Both acute and chronic inflammation also reduced thein vitro plasma protein binding of prednisolone, the reduction being much greater after chronic inflammation. The AUC of free prednisolone after chronic inflammation was 3141 µg · hr/L, compared to 1121 µg · hr/L in the control group and 1823 µg · hr/L after acute inflammation. The mean values of half-life and apparent volume of distribution at steady-state in each group were similar. These results indicate that prednisolone must be used with caution in the treatment of inflammatory diseases because of higher free concentrations of the steroid.     

Nutritional correlates of acute respiratory infections

During October 1992 to June 1993 in eight villages covered by the Primary Health Center Machhra in Meerut District, India, interviews with mothers and examinations of 1600 children aged less than 5 years (under-fives) were conducted to examine the relationship between acute respiratory infection (ARI) and malnutrition. 42.25% of all children had an ARI within the last 15 days. Most ARIs (73.4%) were considered mild (cough and cold with no pneumonia). Pneumonia accounted for 19.5% of all ARI cases, which were considered moderate. The remaining ARI cases were severe (severe and very severe pneumonia). 57.5% of all children suffered from protein energy malnutrition (PEM). 78.6% of children aged 12-14 months had PEM. ARI was more common among malnourished children than well-nourished children (52.2% vs. 28.8%; p 0.001). The incidence of ARI increased as the nutritional status deteriorated (p 0.05). It also increased as the midarm circumference decreased (p 0.001). These findings confirm the synergistic action between malnutrition and infection, in this case ARI. Malnourished children suffer considerable impairment in immunity, especially cellular immunity, which makes them more prone to ARI. These findings reinforce the need to strengthen the quality, quantity, and accessibility of nutritional services, particularly promotion of breast feeding and vitamin A supplementation.     

Determinants of breast feeding practices in rural community of Wardha

In 4 villages of Wardha District in Maharashtra State, India, interviews were conducted with 200 mothers of at least 1 child younger than 12 months so researchers could identify determinants of breast feeding. Most mothers were younger than 25 years (73.5%). The proportion of mothers who initiated breast feeding within 1 hour of childbirth and within 5 hours of childbirth increased as educational level increased. 52.2% of all women initiated breast feeding within 6 hours. Primiparous mothers were less likely to wait 24 hours before breast feeding than multiparous mothers (16.9% vs. 34.5%). Multiparous mothers were more likely to be illiterate than primiparous mothers, which may explain this delay in initiation of breast feeding. As income increased, the likelihood of feeding colostrum to newborns also increased (66.7% for Rs 150, 80% for Rs 200-299, and 85.2% for Rs 300). 28.5% of all women discarded the colostrum. Multiparous mothers were more likely to breast feed for more than 1 year than primiparous mothers (68.5% vs. 31.5%). These findings suggest that increasing the educational level and socioeconomic status of mothers as well as improving the maternal and child health care system by supporting an IEC (information, education, and communication) component in child survival and safe motherhood program will promote breast feeding.     

Practice of prelacteal feeding in a rural community

In India breast feeding in rural areas appears to be shaped by the health beliefs of a community, which are further influenced by social, cultural and economic factors. One of such tradition is prelacteal feeding which is widely prevalent since ancient times. The present study was aimed to find out the practice of prelacteal feeding and various factors which influence this practice. The study on analysis showed that 45% (90) mothers gave prelacteal feeds to their newborns in the form of sugar water, gur water or cow's milk. Sugar water was common amongst mothers belonging to nuclear family (49%) whereas gur water was given mostly by joint family mothers (75.70%). Parity and family type had no significant effect on this practice, however the effect of literacy was found to be significantly related to the practice.     

Effect of the ownership of dialysis facilities on patients' survival and referral for transplantation

BACKGROUND: More than 200,000 patients with end-stage renal disease undergo dialysis in the United States each year, about two thirds in for-profit centers. Economic pressures, such as the decline in inflation-adjusted Medicare payments for dialysis, may compromise the quality of care. Facilities may also be reluctant to refer patients to be evaluated for transplantation because of the loss of revenues from dialysis after patients receive transplants. It is unknown whether for-profit facilities respond more aggressively than not-for-profit facilities to these financial pressures. Therefore, we examined the effect of for-profit ownership of dialysis facilities on patients' survival and referral for possible transplantation. METHODS: We used data from the U.S. Renal Data System to assemble a nationally representative cohort of patients with end-stage renal disease of recent onset. We followed patients for a minimum of three years and a maximum of six years, until death, placement on the waiting list for a renal transplant, or loss to follow-up, or until May 31, 1996. We used proportional-hazards models to assess the effect of the profit status of the dialysis facility on patients' outcomes and adjusted for differences in sociodemographic, clinical, and facility-level characteristics. RESULTS: Of the 3681 patients who were eligible for inclusion, we included 3569 in the analysis of mortality and 3441 in the analysis of the waiting list. The crude mortality rate per 100 person-years of end-stage renal disease was 21.2 for patients treated in for-profit facilities and 17.1 for patients treated in not-for-profit centers (adjusted relative hazard, 1.20; 95 percent confidence interval, 1.02 to 1.42). The likelihood of being placed on the waiting list for a renal transplant was lower for patients treated at for-profit centers (adjusted relative hazard, 0.74; 95 percent confidence interval, 0.56 to 0.98). CONCLUSIONS: In the United States, for-profit ownership of dialysis facilities, as compared with not-for-profit ownership, is associated with increased mortality and decreased rates of placement on the waiting list for a renal transplant.     

Half-ring external fixation in the management of tibial plafond fractures

OBJECTIVE: To investigate the management of tibial plafond fractures with a half-ring external fixator using half pins. DESIGN: Prospective. SETTING: University teaching hospital. PATIENTS: Twenty-four patients with AO Type A or C tibial plafond fractures. OUTCOME MEASURES: Outcome was assessed by using standard criteria of time to union, incidence of infection and malunion, and incidence of pin-tract sepsis. Functional return was assessed by measuring hindfoot function. A scoring system, incorporating clinical and radiological results, was used to rate the results. RESULTS: When using closed or minimally open reduction techniques and interfragmentary screw fixation for the articular component of the fractures, the results of using a half-ring external fixator with half-pins were comparable with those of using small wire fixators. There was a 4.2 percent incidence of infection, and 75 percent of the patients had good or excellent results. CONCLUSIONS: A half-ring external fixator using half-pins produces results that are comparable to those obtained with small wire external fixation. However, the technique is easier and safer.     

Weaning and supplementation practices in a rural community

Weaning and food supplementation practices were examined in a 12-month prospective study of 200 mother-infant pairs from a rural area of Sewagram, India. Only 2 mothers (1%) began weaning before 4 months of age. Between 4 and 6 months, 76 (38%) mothers initiated weaning; at 6 months, this rate was 61%. Illiterate women and mothers with a primary school education, multiparas, and those living in joint families were most likely to defer weaning until after 6 months. Health education campaigns focused on the importance of exclusive breast feeding for the first 4-6 months, followed by the introduction of semisolid foods, are recommended.     

Hyperglycemia and retinopathy of prematurity in very low birth weight infants.

OBJECTIVE: Retinopathy of prematurity (ROP) remains a leading cause of morbidity in the very low-birth-weight (VLBW) infant. This study investigates a possible association between serum/blood glucose and the development of ROP. METHODS: A retrospective case-control study of all infants born between 1992 and 1997 at the Johns Hopkins Hospital with birth weights less than 1000 g who developed Stage 3 or 4 ROP was conducted. Controls either had Stage 1 ROP or no eye disease and were matched 2:1 with ROP patients for gestational age, birth weight and year of birth. Odds ratios (ORs) of ROP were calculated for multiple exposures over the first month after birth, including oxygen concentration (FiO(2)), blood glucose levels, vitamin E, mean airway pressure and mean blood pressure. RESULTS: In a simple logistic regression analysis, we found an increased ROP risk for: (1) each 10 mg/dl increase of mean glucose (OR 1.96; 95% CI 1.13 to 3.42), (2) each 1% increase of mean FiO(2) (OR 1.06; 95% CI 1.004 to 1.13), (3) history of dopamine infusion (OR 5.4; 95% CI 1.16 to 25.2) and (4) intraventricular hemorrhage Grade 3 or 4 (OR 7.3; 95% CI 1.53 to 34.7). Using a multiple regression model, we found an increased ROP risk for each 10 mg/dl increase of mean glucose (OR 2.7; 95% CI 1.003 to 7.27). Each IU/kg/day of vitamin E supplementation reduced ROP risk (OR 0.37; 95% CI 0.16-0.86). CONCLUSION: In this study, we could demonstrate that glucose levels in the first month of life are associated with the development of ROP. Further studies have to determine if this association is causal or if hyperglycemia is just an expression of severity of illness.     

Factors affecting mechanism and kinetics of drug release from matrix-based oral controlled drug delivery systems

Matrix technologies have often proven popular among the oral controlled drug delivery technologies because of their simplicity, ease in manufacturing, high level of reproducibility, stability of the raw materials and dosage form, and ease of scale-up and process validation. Technological advancements in the area of matrix formulation have made controlled-release product development much easier than before, and improved upon the feasibility of delivering a wide variety of drugs with different physicochemical and biopharmaceutical properties. This is reflected by the large number of patents filed each year and by the commercial success of a number of novel drug delivery systems based on matrix technologies. Matrix-based delivery technologies have steadily matured from delivering drugs by first-order or square-root-of-time release kinetics to much more complex and customized release patterns. In order to achieve linear or zero-order release, various strategies that seek to manipulate tablet geometry, polymer variables, and formulation aspects have been applied. Various drug, polymer, and formulation-related factors, which influence the in situ formation of a polymeric gel layer/drug depletion zone and its characteristics as a function of time, determine the drug release from matrix systems. Various mathematical models, ranging from simple empirical or semi-empirical (Higuchi equation, Power law) to more complex mechanistic theories that consider diffusion, swelling, and dissolution processes simultaneously, have been developed to describe the mass transport processes involved in matrix-based drug release. Careful selection of an appropriate model for drug release provides insight to the underlying mass transport mechanisms and helps in predicting the effect of the device design parameters on the resulting drug-release rate. Thus, a basic understanding of release kinetics and appropriate mechanisms of drug release from matrix system and their inter-relationships may minimize the number of trials in final optimization, thereby improving formulation development processes.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.