Primary treatment of pelvic osteosarcoma. Report of five cases.

Five patients, ages 12 to 20 years, with nonresectable primary (Patients 2, 3, and 5) and metastatic (Patients 1 and 4) pelvic osteosarcomas were treated with intraarterial cisplatin and concurrent radiation therapy from 1983 to 1987. Long-term local tumor control was achieved in all five patients. Patients 1 and 3 are alive with no evidence of local recurrence or metastatic disease at 77 and 56 months of follow-up, respectively, since diagnosis of the pelvic tumor. Patients 2, 4, and 5 died of metastatic lung disease at 25, 39, and 12 months, respectively, after diagnosis of the pelvic tumor. Patient 4 had no clinical or radiologic evidence of local recurrence. Control of tumor growth in patients with pelvic osteosarcomas can be achieved with regional chemotherapy and concurrent radiation therapy. These patients also should receive adjuvant intensive systemic chemotherapy to increase the probability of eliminating potential subclinical metastatic disease.     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Calcium ionophore-induced acrosome reaction correlates with fertilization rates in vitro in patients with teratozoospermic semen

The aim of this study was to determine the relationship between calcium ionophore A23187-induced acrosome reaction (AR) and sperm fertilizing ability. Semen samples remaining after preparation for standard IVF were studied in 109 patients who had sperm concentrations > or =20 x 10(6)/ml. Ionophore-induced AR was performed on motile spermatozoa selected by centrifugation on a Percoll gradient. Semen analysis was performed using standard methods. Patients with higher (>50%, n = 76) fertilization rates had significantly higher ionophore-induced AR than patients with lower (<50%, n = 33) fertilization rates (49 +/- 14 versus 38 +/- 21%, P < 0.05). When the data from all patients were analysed by logistic regression, only the percentage sperm motility in insemination medium and ionophore-induced AR were significantly related to fertilization rates. Similar results were also obtained when the data from a subgroup of patients with poor (<15% normal) sperm morphology were analysed. However, when patients with normal sperm morphology > or =15% were analysed separately, only sperm count and the percentage of spermatozoa with progressive motility in semen were significantly related to fertilization rates. In conclusion, ionophore- induced AR was significantly related to fertilization rates in vitro mainly in patients with teratozoospermic semen. Tests for ionophore- induced AR may provide additional information about sperm fertilizing ability but may not indicate specific defects of the physiological AR.      

Intestinal Ca and phosphate transport: differential responses to vitamin D3 metabolites

The transport of Ca and inorganic phosphate (Pi) was studied in the absence of electrochemical gradients across rat intestine in vitro. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the active absorption of both Ca and Pi in all segments of the small intestine, with changes occurring only in absorptive fluxes, whereas secretory fluxes were unaffected. Active Ca absorption was greatest in the duodenum (greater than jejunum greater than ileum) and active Pi absorption was highest in jejunum (greater than duodenum greater than ileum), in agreement with earlier reports. 24R,25-dihydroxy-vitamin2D3 had similar effects on transport but was less potent. The ratios of Pi absorptive fluxes to Ca absorptive fluxes remained remarkably constant during 80-200% increases in absorption produced by 1,25(OH)2D3, suggesting coupled Ca-Pi transport or coordinate stimulation of Ca and Pi absorptive processes by hormonally active metabolites of vitamin D. The results seem most compatible with a differential distribution of vitamin D-responsive Ca and Pi absorptive cells with a predominance of cells with Ca absorptive sites occurring in duodenum, more Pi absorbing cells in jejunum, and a nearly equal ratio of each type in ileum.     

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

Artificial insemination and in-vitro fertilization using donor spermatozoa: a report on 15 years of experience

Donor insemination (DI) using cryopreserved semen commenced at The Royal Women's Hospital in 1976. Over the next 15 years we performed 5953 treatment cycles to achieve 816 pregnancies (13.7% per cycle) and 706 live births. In-vitro fertilization (IVF) using donor spermatozoa commenced in 1986. Over the next 5 years we performed 303 treatment cycles for 185 couples. Including subsequent transfer of cryopreserved embryos, a total of 33% of couples achieved a successful pregnancy by IVF. Statistical analysis indicated that, for DI pregnancies, the most important semen variable was the percentage post-thaw motility, whilst for normal fertilization in IVF it was the pre-freeze motility. These results may be explained by the compensatory effects of post-thaw processing of spermatozoa for IVF, but not for DI in our clinic.      

Depo Provera. Position paper on clinical use, effectiveness and side effects.

Depo Provera (medroxyprogesterone acetate, DMPA) when given as 150 mg by deep intramuscular injection every 12 calendar weeks (84 days+5 days), is a highly effective contraceptive with a very low failure rate comparable to modern copper IUDs and lower than many other methods. It should be available as a first line method to all who wish to make an informed choice about reversible methods of contraception. Pre-use counselling is essential to minimise the effect of menstrual change which occurs in most patients. However there is great patient variability. Use of DMPA is independent of intercourse and also independent of the user's memory (and thus of continuing motivation), other than remembering the 12 weekly appointments. For many women this is a great advantage. Oral contraceptive methods involve remembering to take a pill each day, in the case of the progestogen only pill within the same three hours each day. This places considerable strain on women who lead irregular lifestyles, who are very busy or travel frequently. Such women often describe a constant 'fear of forgetting', especially with the POP. The main potential disadvantage of DMPA in this country are likely to be menstrual disturbance and weight gain. The combined oral contraceptive pill gives the appearance of excellent cycle control because it removes the natural cycle altogether and replaces it with an artificial one. All progestogen-only methods, whether low or high dose, lead to menstrual disturbances, so in this respect DMPA is not unique. Although troublesome, the menstrual disturbances which occur in DMPA users very rarely require operative medical intervention, and can often be improved simply by short courses of oestrogen or shorter injection intervals. Again, women need to know what can be done so that they are aware that they should seek advice early, rather than miserably waiting.for their 12 week appointment. DMPA has no appreciable effects on blood pressure or thrombosis risk. In this it has an advantage over the combined oral contraceptive pill, and provides a simple, effective alternative for women who cannot use the pill for these reasons. Similarly, it has been suggested that women who suffer from focal migraine and are therefore advised against use of the combined oral contraceptive pill can still use progestogen-only contraceptives. Although the POP is medically safe in these circumstances, in young women it is less effective, and involves strict time keeping, which will be disadvantageous for some women. Side effects, long term use and schedules of administration are also discussed. The use of local protocols to allow nurse administration is to be supported both in general practice and the clinic situation. Perhaps the most important issue surrounding the use of DMPA is that of patient information. The method has had a particularly bad public image, which naturally makes potential users anxious and subject to misinformation from poorly informed or biased sources. Also, it is temporarily irreversible during its three months duration, so the duration of any problems or anxieties resulting from side effects may be longer than for other methods. It is of paramount importance that easily understood, accurate patient information leaflets are available, since biased and inaccurate information is readily available from women's magazines, perpetuating the myths surrounding the method.     

Subtalar repositional arthrodesis for adult acquired flatfoot

Arthrodesis of the subtalar joint is well recognized treatment option for moderate or severe flatfoot associated with adult acquired flatfoot secondary to posterior tibial tendon dysfunction. The success of the subtalar arthrodesis is dependent on restoration of normal bony relationships in the hindfoot and midfoot. For this reason, a distinction is made between a repositional arthrodesis and the traditional in situ type of arthrodesis. An in vitro study of the adult acquired flatfoot identifies an anteroposterior subluxation of the subtalar articulation that can be corrected durably and reliably through a repositional talocalcaneal arthrodesis. Intraoperative reduction techniques are useful in obtaining reduction of the peritalar subluxation. There are certain clinical features that help identify patients with flatfoot deformities who are good candidates for subtalar fusion. As the pathoanatomy of the flatfoot deformity is better elucidated, treatment techniques are modified to better address the key elements of the deformity. A repositional subtalar arthrodesis was shown to produce excellent correction in a moderate to severe in vitro flatfoot example in the authors' clinical series.