A sequential treatment regimen with melatonin and all-trans retinoic acid induces apoptosis in MCF-7 tumour cells.

Neoplastic events are marked by uncontrolled cell proliferation. One major focus of cancer research has been to identify treatments that reduce or inhibit cell growth. Over the years, various compounds, both naturally occurring and chemically synthesized, have been used to inhibit neoplastic cell proliferation. Two such oncostatic agents, melatonin and retinoic acid, have been shown to suppress the growth of hormone-responsive breast cancer. Currently, separate clinical protocols exist for the administration of retinoids and melatonin as adjuvant therapies for cancer. Using the oestrogen receptor (ER)-positive MCF-7 human breast tumour cell line, our laboratory has studied the effects of a sequential treatment regimen of melatonin followed by all-trans retinoic acid (atRA) on breast tumour cell proliferation in vitro. Incubation of hormonally responsive MCF-7 and T47D cells with melatonin (10(-9) M) followed 24 h later by atRA (10(-9) M) resulted in the complete cessation of cell growth as well as a reduction in the number of cells to below the initial plating density. This cytocidal effect is in contrast to the growth-suppressive effects seen with either hormone alone. This regimen of melatonin followed by atRA induced cytocidal effects on MCF-7 cells by activating pathways leading to apoptosis (programmed cell death) as evidenced by decreased ER and Bcl-2 and increased Bax and transforming growth factor beta 1 (TGF-beta1) expression. Apoptosis was reflected morphologically by an increase in the number of lysosomal bodies and perinuclear chromatin condensation, cytoplasmic blebbing and the presence of apoptotic bodies. The apoptotic effect of this sequential treatment with melatonin and atRA appears to be both cell and regimen specific as (a) ER-negative MDA-MB-231 and BT-20 breast tumour cells were unaffected, and (b) the simultaneous administration of melatonin and atRA was not associated with apoptosis in any of the breast cancer cell lines studied. Taken together, the results suggest that use of an appropriate regimen of melatonin and atRA should be considered for preclinical and clinical evaluation against ER-positive human breast cancer.     

MID-TRIMESTER MTP USING ENDOCERVICAL PGE2 GEL AND SERIAL INTRAMUSCULAR CARBOPROST

60 cases of mid-trimester pregnancy were terminated using endocervical PGE₂ gel (for achieving cervical priming) followed by serial intramuscular injections of carboprost. In this prospective study, 56 cases were multiparae with gestational age varying between 15-22 weeks. The induction-abortion-interval was 8.4h ± 0.8h with a success rate of 100%. The incidence of incomplete abortion was 5% and check curettage was performed in 16.6% cases. Gastrointestinal side effects were common. Vomiting occurred in 42% cases and diarrhoea in 50%. Febrile morbidity was seen in 8.3% cases. There were no complications of the procedure. The method was highly acceptable to the patients being non-invasive and allowing ambulation throughout. This method of elective mid-trimester abortion is an effective alternative to the other commonly used methods like extra-amniotic ethacridine lactate or intra-amniotic hypertonic saline instillation.KEY WORDS: Carboprost, Mid-trimester abortion, PGE₂     

The effects of surgery on the nitrogen metabolism of parenterally fed human neonates

Nitrogen retention and rates of whole body amino nitrogen flux, protein synthesis, and breakdown were measured in 18 neonates during the 72 h immediately postsurgery. The infants were all intravenously fed with a crystalline amino acid source (Vamin), glucose, and Intralipid The infants were divided into two groups based on amino acid intake: either 2.3 SD 0.4 g or 3.9 SD 0.5 g/kg/day. Nonprotein energy intakes were similar and averaged 81 kcal/kg/day. Group A (n = 11) retained 145 SD 110 mg N/kg/day, whilst group B (n = 7) retained 315 SD 93 mg N/kg/day (p less than 0.001). There were no differences seen in flux, synthesis or breakdown. However, group B had significantly higher net protein synthesis rates (synthesis-breakdown) (p less than 0.01). The improved nitrogen utilization in group B was achieved principally by a reduction in endogenous protein breakdown. There were no differences between the two groups in urinary creatinine or 3-methylhistidine excretion. Since these two parameters reflect skeletal muscle turnover the differences between groups in nitrogen retention and turnover appear to be mediated through visceral protein.     

A randomized prospective trial comparing the value of intravenous and preincisional cefamandole in reducing postoperative sepsis after operations upon the gastrointestinal tract

A prospective randomized trial comparing prophylaxis with a single dose of cefamandole given intravenously and preincisionally with no antibiotics in patients who underwent elective and emergency operations upon the gastrointestinal tract has shown a significant reduction in the frequency of wound infections in patients receiving preincisional antibiotics over both control and intravenous groups. Fewer postoperative infections of the chest occurred in patients receiving antibiotics by either route, with hospital stay also being significantly reduced for patients who received prophylactic antibiotics before emergency operations. Preincisional cefamandole is effective in reducing postoperative sepsis after operations upon the gastrointestinal tract.     

Innovations in teaching obstetrics and gynaecology--the Theme Afternoon

The Theme Afternoon is an exciting and popular new innovation in teaching that we have successfully introduced in Obstetrics and Gynaecology. It utilizes many of the elements of the SCORPIO and SPICES models of teaching. In particular, it involves problem-based learning and an integrated approach to teaching. One afternoon per week is set aside for each theme. So far we have introduced Theme Afternoons in Contraception and Sterilization, The Menopause and Hormone Replacement Therapy, Screening for Disease in O&G and Examination Techniques. All Theme Afternoons follow a similar structure: a targeted tutorial, 10 MCQs, a 15-minute coffee break, OSCEs, and role-play with feedback. An evaluation form is completed by each student assessing the session and the tutor. The Theme Afternoon provides the student with stimulation to learn. It has a wide appeal and has been well received by learners. Students learn at a more controlled pace and in a more sheltered environment, which may be less stressful to them. It evaluates well and is flexible in its structure. The changes that occur are student-led and the desire for it to continue is student-driven. It is easily adaptable to other medical specialties or even nonmedical curriculums. We recommend it as a realistic opportunity to raise standards and enthusiasm in medical education.     

Hyperoxia for management of acid-base status during deep hypothermia with circulatory arrest

BACKGROUND: Which blood gas strategy to use during deep hypothermic circulatory arrest has not been resolved because of conflicting data regarding the advantage of pH-stat versus alpha-stat. Oxygen pressure field theory suggests that hyperoxia just before deep hypothermic circulatory arrest takes advantage of increased oxygen solubility and reduced oxygen consumption to load tissues with excess oxygen. The objective of this study was to determine whether prevention of tissue hypoxia with this strategy could attenuate ischemic and reperfusion injury. METHODS: Infants who had deep hypothermic circulatory arrest (n = 37) were compared retrospectively. Treatments were alpha-stat and normoxia (group I), alpha-stat and hyperoxia (group II), pH-stat and normoxia (group III), and pH-stat and hyperoxia (group IV). RESULTS: Both hyperoxia groups had less acidosis after deep hypothermic circulatory arrest than normoxia groups. Group IV had less acid generation during circulatory arrest and less base excess after arrest than groups I, II, or III (p < 0.05). Group IV produced only 25% as much acid during deep hypothermic circulatory arrest as the next closest group (group II). CONCLUSIONS: Hyperoxia before deep hypothermic circulatory arrest with alpha-stat or pH-stat strategy demonstrated advantages over normoxia. Furthermore, pH-stat strategy using hyperoxia provided superior venous blood gas values over any of the other groups after circulatory arrest.     

Groin hernia repair in Scotland

BACKGROUND: The use of mesh for groin hernia repair has dramatically changed the way this common operation is performed. The aim of this study was to survey the methods of groin hernia repair in Scotland and to assess patient satisfaction with the operation. METHODS: Between 1 April 1998 and 31 March 1999 all patients who underwent groin hernia repair in the National Health Service in Scotland were identified. As well as looking at the type of hernia repair performed and postoperative morbidity, patients were sent a Short Form-36 about 3 months after the operation to assess satisfaction and return to normal activity. RESULTS: Information was obtained on 5506 (97 per cent) of patients who underwent groin hernia repair during the study period. Eighty-five per cent of patients had an open mesh repair and 4 per cent had a laparoscopic repair. Most operations (85 per cent) were performed using general anaesthesia on an inpatient basis (78 per cent), and 8 per cent were for repair of a recurrent hernia. Potentially serious intraoperative complications were rare (seven patients), although they were significantly (P < 0. 001) more likely to be associated with a laparoscopic approach or repair of a femoral hernia: relative risk compared with open inguinal hernia repair 33 (95 per cent confidence interval (c.i.) 6-197) and 22 (95 per cent c.i. 3-152) respectively. Wound complications were common and 10 per cent of patients required a district nurse to attend the wound. Patients expressed a high degree of satisfaction; 94 per cent would recommend the same operation to someone else if required. CONCLUSION: An open mesh repair using general anaesthesia has become the repair of choice for a groin hernia in Scotland. Despite a high incidence of wound complications, patients are satisfied with this operation.     

The treatment of Kawasaki syndrome with intravenous gamma globulin

We compared the efficacy of intravenous gamma globulin plus aspirin with that of aspirin alone in reducing the frequency of coronary-artery abnormalities in children with acute Kawasaki syndrome in a multicenter, randomized trial. Children randomly assigned to the gamma globulin group received intravenous gamma globulin, 400 mg per kilogram of body weight per day, for four consecutive days; both treatment groups received aspirin, 100 mg per kilogram per day, through the 14th day of illness, then 3 to 5 mg per kilogram per day. Two-dimensional echocardiograms were interpreted blindly and independently by two or more readers. Two weeks after enrollment, coronary-artery abnormalities were present in 18 of 78 children (23 percent) in the aspirin group, as compared with 6 of 75 (8 percent) in the gamma globulin group (P = 0.01). Seven weeks after enrollment, abnormalities were present in 14 of 79 children (18 percent) in the aspirin group and in 3 of 79 (4 percent) in the gamma globulin group (P = 0.005). No child had serious adverse effects from receiving gamma globulin. We conclude that high-dose intravenous gamma globulin is safe and effective in reducing the prevalence of coronary-artery abnormalities when administered early in the course of Kawasaki syndrome.