Prevention of delayed emesis caused by chemotherapy.
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Biomedical subjects
Publications and source records attributed to D Harmon.
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Gender is an important risk factor for postoperative nausea and vomiting. Menstrual cycle phase has also been implicated as a further variable in female patients. It is not clear whether a history of an irregular menstrual cycle is a significant variable and studies to date have not examined this. The influence of an irregular menstrual cycle on nausea and vomiting after laparoscopy was evaluated in a blinded, prospective, observational study. One hundred and fifty-nine patients scheduled for laparoscopy and dye investigation were included. Anaesthetic technique and postoperative analgesia were standardised. In comparison with patients who had a regular cycle, an irregular menstrual cycle increased the incidence of nausea or vomiting from 20.5% to 40.5% (absolute difference 20%; 95% CI 0.03-0.37, p = 0.01). Other variables were similar between the groups. An irregular menstrual cycle appears to increase the risk of postoperative nausea and vomiting.
The efficacy of acupressure at the P6 point in the prevention of nausea and vomiting during and after Caesarean section was studied. A double-blind, randomized controlled study of acupressure vs placebo was designed. Ninety-four patients scheduled for Caesarean section were included. The anaesthetic technique and postoperative analgesia were standardized. The use of acupressure reduced the incidence of nausea or vomiting from 53% to 23% compared with placebo (95% confidence interval (CI) 0.34-0.25; P = 0.002) during the operation and from 66% to 36% compared with placebo (95% CI 0.34-0.19; P = 0.003) after the operation. Other variables were similar between the groups.
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The GLIMMER system for microbial gene identification finds approximately 97-98% of all genes in a genome when compared with published annotation. This paper reports on two new results: (i) significant technical improvements to GLIMMER that improve its accuracy still further, and (ii) a comprehensive evaluation that demonstrates that the accuracy of the system is likely to be higher than previously recognized. A significant proportion of the genes missed by the system appear to be hypothetical proteins whose existence is only supported by the predictions of other programs. When the analysis is restricted to genes that have significant homology to genes in other organisms, GLIMMER misses <1% of known genes.
The efficacy of currently available antiemetics remains poor. Concern with their side effects and the high cost of the newer drugs has led to renewed interest in non-pharmacological methods of treatment. We have studied the efficacy of acupressure at the P6 point in the prevention of nausea and vomiting after laparoscopy, in a double-blind, randomized, controlled study of acupressure vs placebo. We studied 104 patients undergoing laparoscopy and dye investigation. The anaesthetic technique and postoperative analgesia were standardized. Failure of treatment was defined as the occurrence of nausea and/or vomiting within the first 24 h after anaesthesia. The use of acupressure reduced the incidence of nausea or vomiting from 42% to 19% compared with placebo, with an adjusted risk ratio of 0.24 (95% CI 0.08-0.62; P = 0.005). Other variables were similar between groups.
Pax7 is a paired-type homeobox gene which has previously been shown to play an important role in skeletal muscle formation. It is expressed in skeletal muscle of the limbs during embryogenesis and in adulthood. The aims of this study were firstly to determine the degree of polymorphism of Pax7 amongst inbred laboratory mice using Southern blotting and Pax7 regional specific sub-probes. Secondly, functional studies were performed on mice with each of the different structural forms of Pax7 to determine whether they were associated with differences in the ability to regenerate damaged skeletal muscle. Four different allelic forms of Pax7 have now been identified in laboratory mice indicating that the previously reported DNA sequence of Pax7 is not applicable to all laboratory mice. Hybridisation patterns of TaqI digested DNA representing each of the different Pax7 alleles with the Pax7 specific sub-probes suggested that in contrast to previous findings, Pax7 is associated with two highly polymorphic homeoboxes. The presence of two homeoboxes in BALB/c mice has been confirmed by DNA sequencing. Results of functional studies have also shown that the ability to regenerate damaged skeletal muscle in adult mice is strongly associated with the presence of a 0.15-kb TaqI fragment derived from one of the homeoboxes.
Structural alterations within the myogenic and neurogenic developmental gene Pax7 which involve TaqI recognition sequences have previously been reported. These alterations are associated with differences in the efficiency of regrowth of damaged skeletal muscle. To identify other structural features of Pax genes which may influence skeletal muscle regrowth, variation in the structure and methylation status of Pax7 and the closely related gene Pax3 has been sought among different mouse strains and during gene expression using the restriction endonucleases MspI and HpaII. Following MspI digestion, RFLPs within Pax7 have been found which most likely reflect intron size variability within the paired box. Differences in the size of MspI and HpaII fragments hybridising with Pax7 and Pax3 region specific sub-probes indicate that the paired boxes are hypomethylated, whereas the region encoding the homeodomain of each gene is highly methylated in the spleen and other tissues from adult mice. In the skeletal muscle precursor cell line C2C12, which expresses Pax7 but not Pax3, the homeodomain encoding region of Pax7 is hypomethylated. In spleen cells, the Pax7 paired box is transcribed but the homeodomain encoding region is not. By contrast, both the paired box and the homeobox of Pax3 are hypermethylated in C2C12 cells indicating that generation of alternate transcripts from Pax genes may be controlled by DNA methylation. In contrast to Pax3, reference to the size of fragments hybridising with a Pax7 homeobox specific probe provides evidence for CpNpG methylation within and immediately downstream from the region encoding the homeodomain. Interestingly, CpNpG methylation remains when the Pax7 homeobox is expressed. Structural variation recognised by MspI digestion and differences in the methylation profile of Pax7 are not associated with the ability to regrow damaged skeletal muscle.
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Charts of 89 osteosarcoma survivors from Massachusetts General Hospital and The Children's Hospital/Dana Farber Cancer Center, who had received primary treatment more than 1 year previously and had no evidence of disease, were reviewed. Sixty-two patients, mean 12 years from diagnosis, agreed to structured interviews. Rates of psychopathology did not differ significantly from the general population. High distress was noted in 13%. Twenty-three normal progeny had been born postchemotherapy to eight women and the wives of five male patients. One pregnancy was complicated by doxorubicin-induced cardiac toxicity. Only two with previous childhood tumors believed themselves infertile. All felt the effort to save the limb was worthwhile. In most, ongoing pain was mild; phantom pain and neuralgia common. Most survivors were in good mental and physical health with the capacity to bear children.
The relation of acute thrombocytopenic purpura (TP) to the use of drugs was investigated in a case-control study conducted in eastern Massachusetts, Rhode Island, and the Philadelphia region; 62 cases over the age of 16 years with acute onset and with a rapid recovery were compared with 2,625 hospital controls. After control for confounding by multiple logistic regression, use of the following drugs in the week before the onset of symptoms was significantly associated: trimethoprim/sulfamethoxazole (relative risk [RR] estimate, 124), quinidine/quinine (101), dipyridamole (14), sulfonylureas (4.8), and salicylates (2.6). The overall annual incidence of acute TP was estimated to be 18 cases per million population. The excess risks for the associated drugs were estimated to be 38 cases per million users of trimethoprim/sulfamethoxazole per week, 26 per million for quinidine/quinine, 3.9 per million for dipyridamole, 1.2 per million for sulfonylureas, and 0.4 per million for salicylates. Associations with sulfonamides, quinidine/quinine, sulfonylureas, and salicylates have been previously reported, but the present study has provided the first quantitative measures of the risk. The association with dipyridamole was unexpected. In general, despite large RRs, the incidence rates attributable to the drugs at issue (excess risks) were low, suggesting that TP is not an important consideration in the use of the various drugs.
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The clinical course of 117 patients who were treated for Stages IIB-IIIC sarcoma of soft tissues by the combined approach of radiation and surgery at MGH during the period 1971-1984 have been analyzed for an effect of adjuvant chemotherapy to improve clinical results. Thirty-two patients received adjuvant chemotherapy and 85 were treated by local methods alone. The chemotherapy protocols featured doxorubicin (25 patients) or VAC (seven patients). The no chemotherapy patients were controls matched for tumor grade and size and were treated over approximately the same period. The two groups were not well matched for age: median age of 38.5 and 54 years for the treated and control groups, respectively. There was no significant difference in survival. However, the time to first metastasis was longer in the treated group, P = 0.04. Furthermore, the local failure rate appeared to be lower in the treated group, P = 0.06.
One hundred fifty patients with bone marrow failure were treated in three groups with antithymocyte globulin (ATG; Upjohn, Kalamazoo, MI) in a multicenter trial. Patients were assessed at 3, 6, and 12 months after initiation of treatment by three criteria: transfusion independence, clinical improvement, and blood counts. Group I consisted of 77 patients with acute severe aplastic anemia, randomized to receive either ten or 28 days of ATG. There was no significant difference between the two arms of this protocol: 47% of all patients were clinically improved and 31% were transfusion independent at 3 months. Of the severely affected patients, 27% died before 3 months; most deaths occurred early in treatment. Factors associated with survival in severely affected patients included male sex, age less than 40 years, absolute neutrophil count greater than 200/microL, and idiopathic etiology. Neutrophil counts generally increased by 8 weeks after treatment, but patients continued to show improvement to 1 year posttreatment. In Group II, 44 patients with moderate or chronic severe aplastic anemia were randomized to receive either ten days of ATG or 3 months of high-dose nandrolone decanoate. No patient initially treated with androgens recovered, but 28% of ATG-treated cases achieved transfusion independence at 3 months. Group III consisted of patients with a variety of bone marrow failure syndromes. Patients with pancytopenia and cellular bone marrow showed response rates similar to those of patients with chronic or moderate aplastic anemia.
The colon motor response to a meal consisting of 100 mM of sodium oleate was assessed before and after neodecortication in male Sprague-Dawley rats. Recording probes were anchored surgically in the ascending and descending colon. Pressure changes were recorded on a dynograph using a low-compliance perfusion system. A motility index took into account the amplitude, duration, and frequency of contractions. Neodecortication increased the motility index of the distal colon in the fasting state. However, removal of the cerebral cortex did not affect significantly the colon motor response to a meal. Meal stimulation increased the motility index before and after neodecortication. These findings suggest that resting colonic motor activity is increased after neodecortication, probably through the loss of an inhibitory influence of the central nervous system; and the cerebral cortex is not required for the colon response to a meal in the rat.