Menstrual patterns leading to the final menstrual period.

OBJECTIVE: To characterize premenopausal menstrual regularity and the patterns of divergence from regularity associated with the approach of the final menstrual period. DESIGN: Two samples of individual cycle length sequences contributed by participants in a population-based longitudinal study of the menopausal transition were examined. The first sample, of "early" sequences, is used to characterize menstrual regularity. The second shows how cycle length patterns change as the final menstrual period (FMP) is approached. Regression slopes are used to measure trend in cycle length, and changes in cycle length variability are registered by a simply calculated measure, the "running range." RESULTS: Sequences in the early cycles sample rarely varied outside the 21-35 day range and did not show a rising or falling trend. In contrast, pre-FMP sequences generally became increasingly variable in length, while rising above 35 days in mean during the last 10 cycles. The variability measure remained below 40 days throughout the early sequences, but characteristically rose above 42 days during sequences including the last 20 pre-FMP cycles. In early sequences, but not in pre-FMP sequences, long and short cycles tended to alternate. CONCLUSIONS: Increased variability is the dominant feature of cycle length pattern for most women as their final menstrual period approaches. Underlying this is a steady trend toward mean cycle lengths above 35 days. An indicator of the approach of menopause is a rise in running range of cycle lengths to 42 days.     

Emergent right hemicolectomies

Emergent right hemicolectomies have historically been associated with surprisingly high morbidity and mortality rates. A retrospective review of emergent right hemicolectomies over a 7-year period was performed to assess current morbidity and mortality. Emergent right hemicolectomy was defined as a procedure performed for an acute abdomen with no formal preoperative cleansing of the colon. Demographic data, diagnostic evaluation, length of stay and outcomes were evaluated. Over the study period, 122 emergent right hemicolectomies were performed on both general surgery and trauma patients. The average patient was 52.9 +/- 18.5 years old, and the majority of patients (66.4%) were male. The indications for the procedures performed were bowel perforation (51), hemorrhage (25), cancer (16), benign obstruction (14), phlegmon (8), ischemia (6), or other (2). Resection with primary anastomosis was performed in 98 patients, 16 had an end ileostomy, and 8 underwent damage control procedures in which gastrointestinal continuity was not reestablished at the time of the original operation. Postoperative complications developed in 48 patients (39.3%). The majority of the complications (83.3%) were related to infection including intra-abdominal abscess (21 patients), sepsis (16), and wound infection (5). Other complications included anastomotic leak (5), wound dehiscence (3), stoma-related (3) and postoperative bowel obstruction (2). The patients who developed complications did not differ from those who had an uneventful postoperative course in terms of age, indication for procedure, or presence of intraabdominal abscess or gross contamination at the time of the original procedure. The overall mortality rate was 13 per cent. Patients who died were older than those who lived (63 +/- 19 vs 52 +/- 18; P = 0.03) and were significantly more likely to have evidence of shock on presentation (P = 0.0013). Emergent right hemicolectomies continue to be associated with high morbidity and mortality rates. The most common complications are related to infection. Age and manifestations of shock at the time of admission are strong predictors of mortality.     

Complementary antineoplastic activity of the cytosine nucleoside analogues troxacitabine (Troxatyl) and cytarabine in human leukemia cells

Purpose Troxacitabine (BCH-4556, l-(–)-OddC, Troxatyl) is a novel -l-nucleoside analogue with potent antineoplastic activity both in vitro and in several tumor models in vivo, and is presently in phase II clinical trials. The combination of the cytosine analogues troxacitabine and araC (1--d-arabinofuranosylcytosine, cytarabine) has shown promising activity in patients with acute myelogenous leukemia. To further examine the interactions between these two analogues, we investigated the in vitro and in vivo effects of their combination against a human leukemia cell line, CCRF-CEM.Methods The in vitro cytotoxic effect of the combination of troxacitabine and araC on the survival of CCRF-CEM cells was measured using a standard MTT assay and combination indices were generated with the CalcuSyn software. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on survival of CCRF-CEM tumor-bearing animals. Mechanistic studies addressed recovery of DNA synthesis, intracellular levels of araC metabolites, feedback inhibition by triphosphate species and pharmacokinetics of both drugs.Results The combination of troxacitabine and araC in vitro was synergistic with combination indices between 0.1 and 0.7. This appeared to be related to the impact of the combination on DNA synthesis recovery, which was significantly delayed following exposure to the combination of troxacitabine and araC compared to either agent alone. Analysis of the effect of troxacitabine on the intracellular metabolites of araC revealed that troxacitabine did not inhibit araC deamination and caused a slight decrease in the overall intracellular accumulation of araCTP. The lower accumulation of araCTP could not be attributed to feedback inhibition caused by troxacitabine triphosphate on dCK. Furthermore, our in vivo experiments demonstrated that the combination of araC and troxacitabine was better at slowing down the progression of leukemia in SCID mice than either agent used alone without additive toxicities. Injections of 10 mg/kg troxacitabine i.p. daily for 5 days in combination with araC at 10 mg/kg led to an increase in median survival time of 58 days compared to 49.5 and 53.5 days for araC and troxacitabine, respectively, given as single agents. This represents an increase in life span of 17%, respectively when compared to araC alone. A pharmacokinetic study revealed that troxacitabine did not influence the disposition of araC when coadministered.Conclusions Overall, our results show that the antileukemic activity of troxacitabine and araC is complementary when the two nucleoside analogues are combined in vivo. These effects appear to be related to their interaction at the level of DNA repair rather than to pharmacokinetic interactions. These results encourage the use of troxacitabine and araC in combination in patients with acute leukemia.Abbreviations AML Acute myelogenous leukemia - araC 1--d-Arabinofuranosylcytosine, cytarabine - araCMP Cytarabine-5-monophosphate - araCTP Cytarabine-5-triphosphate - araU 1--d-Arabinofuranosyluracil - dCyd Deoxycytidine - CDA Cytidine deaminase - CI Combination index - dCK Deoxycytidine kinase - dCTP Deoxycytidine-5-triphosphate - dFdC Gemcitabine, 2,2-difluorodeoxycytidine - troxacitabineTP Troxacitabine 5-triphosphate     

Mitochondria: biogenesis,structure, and function--symposium introduction

During the past three to four decades, a significant amount of data was collected to reinforce the notion that mitochondrial function is irrevocably linked to mitochondrial structure. Indeed, data from numerous studies have revealed several salient points of mitochondrial biology that include the following: 1). mitochondria exist as a reticulum rather than as single entities, 2). different mitochondrial populations identified by their cellular location are characterized by different structural and functional characteristics, and 3). muscle mitochondrial respiratory capacity readily adapts to changes in muscle use and disuse by adjusting tissue metabolic capacity to match functional demands. More recently, research in the area of mitochondrial biology has focused on uncovering 1). the cellular signals responsible for the control of mitochondrial biogenesis via coordinate regulation of nuclear and mitochondrial gene expression, 2). the mechanisms by which mitochondrial respiration is regulated, and 3). the role of mitochondria in apoptotic cell death. The most current knowledge in these areas of mitochondrial biology will be addressed in the following symposium papers.     

Quality of life after gastric transposition for oesophageal atresia

Background/Purpose: A small proportion of infants born with oesophageal atresia in which the gap between the 2 ends of the oesophagus is too great for an end-to-end anastomosis will require oesophageal replacement. Since 1981 the author's procedure of choice for oesophageal replacement has been gastric transposition. The long-term functional outcome appears to be satisfactory, but the quality of life of these patients has not been investigated formally. This report assesses the health-related quality of life (QOL) of 2 groups of patients born with oesophageal atresia who have undergone gastric transposition. Methods: The study group comprised 28 patients aged 2 to 22 years who resided in England. Group 1 (n = 13), comprised patients who had undergone cervical oesophagostomy and gastrostomy without attempt at oesophageal anastomosis; group 2 (n = 15), comprised patients who had undergone previous attempts at reconstruction or replacement. QOL was assessed using modified versions of the Gastrointestinal Quality Of Life Index (GIQLI). Results: QOL scores based on patients' responses showed no significant differences between the groups (124 v 119). However, the disease-specific symptom scores showed that patients in group 1 experienced fewer symptoms compared with those in group 2. Additionally, based on parental responses, patients in group 1 had higher QOL scores than those in group 2. QOL scores for patients aged 2 to 4 years (n = 5) did not differ between the groups (81 v 92, not significant). Conclusions: The quality of life for patients with oesophageal atresia undergoing gastric transposition was generally unimpaired by any side effects of gastric transposition. Patients undergoing gastric transposition as a primary procedure experienced fewer disease-specific symptoms in the medium term compared with patients who had undergone previous unsuccessful attempts at reconstruction or replacement of their oesophagus. J Pediatr Surg 38:53-57.