Potential role of reactive metabolites of addictive drugs at the receptor: a novel hypothesis

The central nervous system (CNS) stimulants to CNS depressants such as morphine, cocaine, methamphetamine and nicotine each have the capacity for inducing chemical dependence with an enormous impact on human behavior. Because of the difficulties in isolation, the role of the reactive metabolites as a modulating factor in the receptor activation and related addiction of these drugs is not studied. The chemical transformations of these compounds to their metabolites at the receptors have been proposed. There is the distinct possibility that irreversible binding of N-hydroxy, N-formyl or related metabolites of morphine, cocaine, methamphetamine, or nicotine with the respective receptors can occur. This unique role of highly reactive molecular species is postulated. In this way, the synaptic glutaminergic and or dopaminergic transmission can be compromised. On repeated exposure of the drug, the receptor reserve may decrease. More drug is needed to activate the residual receptor to maintain the reward in addiction.     

Calcium carbonate gallstones in children

Background

In the United States, cholesterol stones account for 70% to 95% of adult gallstones and black pigment stones for most of the remainder. Calcium carbonate stones are exceptionally rare. A previous analysis of a small number of pediatric gallstones from the north of England showed a remarkably high prevalence of calcium carbonate stones. The aims of this study were to analyze a much larger series of pediatric gallstones from our region and to compare their chemical composition with a series of adult gallstones from the same geographic area.

Methods

A consecutive series of gallbladder stones from 63 children and 50 adults from the north of England were analyzed in detail using Fourier transform infrared microspectroscopy. Demographic and clinical data were collected on all patients. The relative proportions of each major stone component were assessed: cholesterol, protein and calcium salts of bilirubin, fatty acids, calcium carbonate, and hydroxyapatite.

Results

Thirty-nine (78%) adults had typical cholesterol stones, 7 (14%) had black pigment bilirubinate stones, and only 2 (4%) had calcium carbonate stones. In contrast, 30 (48%) children had black pigment stones, 13 (21%) had cholesterol stones, 15 (24%) had calcium carbonate stones, 3 (5%) had protein dominant stones, and 2 (3%) had brown pigment stones. In children, cholesterol stones were more likely in overweight adolescent girls with a family history of gallstones, whereas black pigment stones were equally common in boys and girls and associated with hemolysis, parenteral nutrition, and neonatal abdominal surgery. Calcium carbonate stones were more common in boys, and almost half had undergone neonatal abdominal surgery and/or required neonatal intensive care.

Conclusion

The composition of pediatric gallstones differs significantly from that found in adults. In particular, one quarter of the children in this series had calcium carbonate stones, previously considered rare. Geographic differences are not the major reason for the high prevalence of calcium carbonate gallstones in children.     

Successful treatment of chronic hepatitis C with pegylated interferon in combination with ribavirin in a methadone maintenance treatment program

Injection drug users constitute 60% of the more than 4 million people in the United States with hepatitis C virus (HCV), including many methadone maintenance patients. Few data exist describing clinical outcomes for patients receiving HCV treatment on-site in methadone maintenance settings. In this retrospective study, we describe clinical outcomes for 73 patients receiving HCV treatment on-site in a methadone maintenance treatment program. Fifty-five percent of patients achieved end-of-treatment response, and 45% achieved sustained viral response. These treatment response rates are nearly equivalent to previously published HCV treatment response rates, despite high prevalences of ongoing drug use (49%), psychiatric comorbidity (67%), and HIV coinfection (32%). These data show that on-site HCV treatment with pegylated interferon and ribavirin is effective in methadone-maintained patients, many of whom are active drug users, psychiatrically ill, or HIV coinfected, and that methadone maintenance treatment programs represent an opportunity to safely treat chronic hepatitis C.     

Surgical management of large adrenal tumours: the University of Miami experience using liver transplantation techniques

OBJECTIVE

To report our experience in the surgical management of patients with large adrenal masses and describe the key steps in performing radical resections, which are especially demanding where thrombi extend into the inferior vena cava (IVC).

PATIENTS AND METHODS

From 2003 to 2007, 14 patients presented with large adrenal mass, and underwent surgical extirpation. In five patients thrombi extended into the IVC, causing Budd–Chiari syndrome in one.

RESULTS

The median (range) patient age was 48 (40–58) years. The excision was radical with negative tumour margins in all cases. Cardiopulmonary bypass (CPB) was required in one case with adherent intra‐atrial thrombus. The mean blood loss was 500 (250–1500) mL except in the patient who required CPB. Morbidity included pleural effusion (three patients) and postoperative pneumonia (two), which responded to conservative management. All patients were alive and free of disease at a median follow‐up of 12 (5–42) months.

CONCLUSIONS

Surgical extirpation of large adrenal masses requires technical experience to optimize outcome. Total tumour excision is the only therapeutic option in such cases and provides acceptable results in survival and quality of life.     

Modified Pfannenstiel approach for radical retropubic prostatectomy: a 3-year experience

A modified Pfannenstiel approach for radical retropubic prostatectomy (RRP) has been described previously. We present our experience with this approach for performing a RRP over the past 3 years. Between January 2003 and July 2006, 544 consecutive RRPs by modified Pfannenstiel approach between January 2003 and July 2006 were performed. We analyzed blood loss, transfusions, use of drain, pain score, analgesia and hospital stay. Patients were followed up at 6 weeks, three monthly for a year and six monthly thereafter. All clinical and operative variables were entered into a database and analyzed. A total of 544 men underwent RRP with median follow-up of 11 (s.d.+/-10.5) months. The mean age was 60 (s.d.+/-7) years. About 83, 91 and 95% of patients had nerve sparing, bladder neck preservation and a lymph node dissection, respectively. Fifty-three patients had a concurrent inguinal hernia repair through the same incision. Mean estimated blood loss was 431 (s.d.+/-267) ml. The pathological staging distribution was T2, 82%; T3a, 9%; and T3b, 9%. The mean pain score at days 1 and 7 were 3.7 (s.d.+/-2.5) and 3.3 (s.d.+/-3), respectively. The median hospital stay was 36 h (s.d.+/-24). About 5.5% have had biochemical recurrence. At 12 months 97% were continent and 46% potent. RRP using a modified Pfannenstiel approach offers safety and efficacy. It facilitates repair of associated inguinal hernia through the same incision.