Renal electrolyte and fluid handling in the rat following chloroquine and/or ethanol administration

We postulated that chloroquine and/or ethanol affect plasma arginine vasopressin (AVP) concentrations to alter renal function. Therefore, we studied the effects of chloroquine and/or ethanol on plasma AVP concentrations and fluid, urinary Na(+) and K(+) outputs in separate groups of anaesthetized Sprague-Dawley (SD) rats challenged with a continuous jugular infusion of 0.077 M NaCl at 150 microl.min(-1). After a 3-h equilibration period, vehicle, chloroquine (0.06 microg. min(-1)), ethanol (2.4 or 24 microg.min(-1)) or both chloroquine and ethanol were added to the infusate after 1 h (control) for 1 h 20 min (treatment). The animals were switched back to the infusate alone for the final 1 h 40 min recovery periods. Urine flow Na(+) and K(+) excretion rates were determined at 20-min intervals over the subsequent 4-h postequilibration period. Blood was collected from separate groups of animals at the end of treatment period or equivalent time for control animals for measurement of plasma aldosterone and AVP concentrations by radioimmunoassay. Simultaneous chloroquine and ethanol infusion significantly (p < 0.01) increased plasma chloroquine concentrations in an ethanol dose-dependent manner by comparison with animals administered chloroquine alone. Chloroquine infusion alone (0.06 microg.min(-1)) and/or ethanol (2.4 or 24 microg.min(-1)) elevated plasma AVP concentrations from 9.73 +/- 1.64 fmol.l(-1) in control rats to 15.65 +/- 2.49 fmol.l(-1), 17. 39 +/- 4.21 fmol.l(-1), and 33.87 +/- 6.18 fmol.l(-1), respectively. Separate administration of chloroquine or ethanol at low dose rates increased urinary Na(+) excretion rates. We conclude that the impairment of renal electrolyte handling associated with chloroquine administration may be exacerbated by ethanol.     

Klebsiella pneumoniae with extended spectrum beta-lactamase activity associated with a necrotizing enterocolitis outbreak

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in newborn infants, affecting primarily premature neonates. Clustering of cases in epidemics is well-described; many are associated with an identifiable pathogen. PATIENTS AND METHODS: Case reports are presented of six neonates seen with NEC during a 2-month period in 1998. All bacterial isolates were subjected to antibiotic testing, determination of MIC and molecular fingerprinting. RESULTS: Klebsiella pneumoniae with extended spectrum beta-lactamase production was isolated from blood cultures of all six patients. In five patients the isolate appeared to be a single clone. The onset of NEC in the patients was earlier, more rapid and more severe than usual. Four of the six required surgery and five required mechanical ventilation. Two of the six patients died, but only one was directly related to a complication of NEC. All of the patients developed severe thrombocytopenia (platelet count <20 x 10(9)/l), and three developed hepatitis. The K. pneumoniae proved difficult to eradicate. Extended courses of multiple antibiotics were administered and measures were introduced to reduce overcrowding and improve infection control. CONCLUSION: The isolation of a single clone of K. pneumoniae with extended spectrum of beta-lactamase activity during an NEC outbreak highlights the need for strict infection control. This organism caused significant morbidity and was difficult to treat.     

Prolactin response to the severity of surgical insult.

Prolactin levels are elevated significantly during the recovery process from surgical insult, implying a role for prolactin in the neuroendocrine immune network. This study examined the importance of severity of surgical insult to the prolactin response. Two groups of surgical patients were chosen consecutively and studied prospectively. Seven patients scheduled for "clean" elective surgery, i.e., herniorrhaphy and laparoscopic cholecystectomy, were compared with seven patients scheduled for prolonged abdominal exploration. Blood was drawn for prolactin and cortisol at 8:00 AM on the day of surgery and on postoperative days one, three, and five. Using a two-tailed test, preoperative prolactin levels and levels on postoperative days three and five were significantly different in the prolonged surgery group (.012 and .002, respectively). There were no statistically significant differences in preoperative and postoperative prolactin levels in the clean surgery group. Cortisol levels were not significantly elevated in either group. These results indicate that the prolactin response to surgery is related to the severity of the surgical insult.     

Tumour-specific distribution of BRCA1 promoter region methylation supports a pathogenetic role in breast and ovarian cancer

The role of BRCA1 in sporadic breast and ovarian cancers remains elusive. Direct involvement of BRCA1 in the development of breast and ovarian cancer is suggested by the finding that the BRCA1 promoter region CpG island is methylated in a proportion of breast and ovarian cancers. The aim of this study was to compare the incidence of BRCA1 promoter region methylation in tumours in which loss of BRCA1 has been shown to play a role in pathogenesis (breast and ovarian carcinomas) with the incidence in tumours in which BRCA1 is unlikely to play a role in pathogenesis. Promoter region hypermethylation was significantly more common (P < 0.008) in breast and ovarian cancer (6/38 tumours methylated) than in colon cancer (0/35 tumours methylated) or in leukaemias (0/19 samples methylated). The restriction of BRCA1 promoter region hypermethylation to breast and ovarian cancer is consistent with a pathogenetic role of BRCA1 promoter methylation in these tumours. We suggest that the rarity of observed BRCA1 mutations in sporadic breast and ovarian cancer is due to the greater likelihood of BRCA1 inactivation by non-mutational mechanisms such as methylation.     

Spinal Cord Astrocytomas: Presentation, Management and Outcome

Intramedullary spinal cord astrocytomas are uncommon tumors. They are the most common spinal cord tumor in children and in adults are second only to ependymomas in frequency of occurrence. Low-grade histology predominates with high-grade lesions comprising only ten to fifteen percent of pediatric tumors and a slightly higher proportion in adults. Presenting symptoms typically evolve over months to years with regional back pain the most commonly reported initial complaint. Malignant tumors produce rapid neurological deterioration. MRI is the diagnostic modality of choice: spinal cord astrocytomas are iso- to slightly hypointense on T1, hyperintense on T2 and commonly have associated cysts. They enhance less intensely and are more eccentric than ependymomas. The goals of surgical intervention are to obtain a tissue diagnosis and resect as much tumor as possible without adversely affecting neurological function. Astrocytomas are infiltrating neoplasms and total resection is not generally possible. Somatosensory and motor evoked potential monitoring are routinely used but it is unclear if they improve outcomes. The operating microscope and bipolar cautery are essential surgical tools; the ultrasound and ultrasonic surgical aspirator are useful surgical adjuncts. Laminectomy is performed on adults while laminoplasty is favored for pediatric patients. Outcome for low-grade astrocytomas is less favorable than that of ependymomas with regard to both recurrence and function though many have prolonged survival. There is no correlation of extent of resection and recurrence. Outcome for high-grade tumors is extremely poor; tumor progression is relentless; median survival is thirteen months in children and six months in adults.     

Radiation Therapy Oncology Group (RTOG) trials for head and neck cancer

Clinical investigations for cancer of the head and neck, primarily tumors of the upper respiratory and digestive tracts, have been one of the most important components of the Radiation Therapy Oncology Group (RTOG) since its inception 30 years ago. Emphasis from the very beginning to the present time has been on altered fractionation. Studies of hypoxic cell sensitizers were also explored for many years. More recently, combinations of radiation therapy with cytotoxic chemotherapeutic agents, either sequentially or concurrently, have been a major focus. Although the majority of the trials have been for unresectable tumors, surgical adjuvant radiation therapy alone or combined with chemotherapy has also been an important activity. Combined modality trials emphasizing organ conservation have been carried out within the last decade. The RTOG represents a national and international resource for studies of cancer of the head and neck. Its results influence the care of patients and the clinical research environment.     

Primary pancreatic lymphoma: a case report, literature review, and proposal for nomenclature

Primary neoplasms of the pancreas are most often adenocarcinoma. Non-Hodgkin's lymphoma (NHL) involving the pancreas is less common but well documented; the pancreas as the primary site of NHL is rare. The majority of patients with pancreatic cancer, whether it is adenocarcinoma or lymphoma, present with a mass in the head of the gland. Pancreatic lymphoma is often described as a large homogeneous mass with extra-pancreatic extension, with or without associated lymphadenopathy. Less common presentations are masses in the body or tail, or more rarely diffuse involvement of the pancreas. We present a case of diffuse pancreatic lymphoma with extra-pancreatic dissemination to the spleen and lymph nodes, and review the literature on pancreatic lymphoma. Because the definition of pancreatic lymphoma and primary pancreatic lymphoma varies, we also propose a nomenclature system to make future studies of pancreatic lymphoma more comparable.     

The post-operative mortality of ruptured abdominal aortic aneurysm repair.

INTRODUCTION: Late peri-operative death after ruptured abdominal aortic aneurysm (RAAA) repair is usually due to multiple-organ failure. The aim of this study was to identify any factors that are associated with mortality in this group of patients. METHODS: A retrospective case-note review of a single decade's operative experience of RAAA repair in a single centre. Only those patients with confirmed rupture at laparotomy were included. Sixty-three pre- intra- and post-operative variables were recorded where possible for each patient who survived surgery and the initial 24-hours post-operatively. Multi-variate analysis was performed using stepwise logistic regression. The P-POSSUM, RAAA-POSSUM, RAAA-POSSUM (physiology only), V-POSSUM, and V-POSSUM (physiology only) models were all compared to determine how each performed in these patients. RESULTS: Two hundred and twenty-three cases of confirmed RAAA were identified, of whom 139 survived the operation and initial 24-hours post-operatively. In-hospital mortality in this group of patients was 32.4%. Variables significantly associated with mortality after multi-variate analysis, were low intra-operative systolic blood pressure, the presence of a consultant anaesthetist at the initial operation and the development of cardiac, renal or gastro-intestinal complications. All POSSUM models except the V-POSSUM and P-POSSUM (physiology only) models demonstrated no significant lack of fit in this dataset. DISCUSSION: Factors associated with delayed peri-operative death after RAAA are not the same as those previously found to be associated with overall peri-operative mortality after RAAA repair.     

Drug treatment of Alzheimer's disease

Drugs may be part of the treatment for Alzheimer's disease. Drug treatment can be divided into two categories: treatment to improve cognitive function and treatment to improve abnormal behaviors. There are at least 16 new drugs undergoing evaluation that may improve cognitive function. Some of these drugs are intended to augment acetylcholine neurotransmitter function. Others are nootropics that affect neuron metabolism with little effect elsewhere. A third major category is drugs that affect brain vasculature. A miscellaneous group includes drugs aimed at modifying other defects found in Alzheimer's disease. Drugs to affect behavior have been available for some time. These include neuroleptics, anxiolytics, and antirage drugs. Use of all these drugs has been controversial. Recent federal legislation and guidelines affect their use in nursing homes. Specific indications for neuroleptics are psychotic features and agitation. Dosage for patients with dementia is different than for other psychotic patients. There is no consensus on the use of other psychoactive medications.