Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Inhibin and renin in follicular fluids of patients with one or two ovaries stimulated with a GnRH agonist and gonadotrophins

Follicular fluids from eight patients with one ovary and from ten patients with two ovaries were investigated for bioactive inhibin, total renin, oestradiol (E2) and progesterone (P4) concentrations. Four follicular fluids were pooled per patient before assessment. All women had been stimulated similarly using a protocol including a GnRH agonist, HMG and HCG. Renin levels were significantly lower and P4 significantly higher in pools of follicular fluid from patients with one ovary, whereas inhibin and E2 concentrations were similar in both patient groups. A significant negative correlation was found in the pools of follicular fluid between inhibin and E2 in both groups. These results suggest a role for inhibin and renin in the paracrine and autocrine control of stimulated follicular development.     

Rate-sensitive glucocorticoid feedback inhibition of adrenocorticotropin and beta-endorphin/beta-lipotropin secretion in rats

In the present study, we present physiological evidence for rate-sensitive, fast feedback inhibition of secretion of ACTH and beta-endorphin (beta END)-related peptides. We used a 2 min restraint stress to physiologically increase plasma corticosterone, then examined the plasma responses of immunoreactive ACTH and beta END plus beta-lipotropin (beta END/beta LPH) to a subsequent restraint stress. After onset of this stress, plasma corticosterone increased from 2.5-10 min at a rate of 120 nM min-1, then remained at a peak from 10-15 min. A single 2 min restraint stress produced peak plasma levels of ACTH and beta END/beta LPH 2.5 min after onset of the stress, and these plasma concentrations declined after this initial stress at rates of 2.7 and 7.4 pM min-1, respectively. Application of a second restraint stress at the time of the peak corticosterone response produced plasma ACTH and beta END/beta LPH responses similar to those after the first stress. Application of a second stress during the period of significant rate-rise of corticosterone in plasma did not result in decreased incremental responses of plasma ACTH or beta END/beta LPH. However, the rates of decline of plasma ACTH and beta END/beta LPH of 7.6 and 32 pM min-1, respectively, from peak levels, were significantly greater after this second stress applied during the period of significant increase in plasma corticosterone concentration than the corresponding rates of decline observed after the initial stress or after a subsequent stress applied at the peak of plasma corticosterone. These differences in rates of decline of plasma ACTH or beta END/beta LPH appear to reflect differences in secretion rate rather than clearance, since disappearance of [125I]ACTH1-24 was not different after an initial vs. subsequent stress. In contrast to these data from intact rats, initial and subsequent stresses did not show different rates of decline of plasma ACTH or beta END/beta LPH in adrenalectomized rats. In conclusion, the stress-induced rate rise of glucocorticoid provides a negative feedback signal which serves to terminate and limit the duration, but not the peak, of the responses of POMC-derived peptides to subsequent stress.     

Cerebellar tumour presenting with pathological laughter and gelastic syncope

There is no report of patients in whom pathological laughter, a rare condition characterized by uncontrollable episodes of laughter usually triggered by unrelated stimuli, was ever closely associated with a loss of consciousness overtly linked with the onset of such uncontrollable laughter, also referred to as a gelastic syncope. A 53-year-old man presented with a 4-month history of syncope following intense and uncoordinated laughter. Physical and neurological examination was normal and the patient had no other typical cerebellar signs. We found a mass in the cerebellar vermis abutting the floor of the fourth ventricle, which upon histological examination after surgery proved to be an ependymoma. We emphasize that pathological laughter and gelastic syncope could represent unique and sole features of a cerebellar disorder.     

Provision of immunisation--the Gazankulu experience

Following the outbreak of poliomyelitis in Gazankulu in 1982, the immunisation services in Gazankulu were thoroughly examined. As a result of this, a comprehensive immunisation policy for Gazankulu was accepted in November 1986. The broad aim of the policy is to provide effective immunisation to all Gazankulu residents against tuberculosis, diphtheria, pertussis, tetanus, poliomyelitis and measles. A specific objective is that by the end of 1987, 85% of under-5s should have been vaccinated against these six diseases and by the end of 1990 this percentage should be 97%. The detailed strategies to reach these objectives are highlighted. Within the framework of the objectives, the policy allows different areas to formulate individual strategies. Programme monitoring and community involvement are two crucial aspects of the policy and these are discussed in detail. The early successes and difficulities in implementing this policy are discussed.     

Breast feeding practices--impressions from an urban community.

Information regarding breast feeding practices of 600 children below 3 years of age attending hospital OPDs and private clinics during 1984-85 were collected. 51.3% received breast milk within 24 hrs. of birth, mean duration of breast feeding being 6 months. 68% of Infants had been given prelacteal feeds. 34% children were exclusively breast fed till 1 month. Insufficient milk was an important reason for discontinuation before 6 months.     

Cellular events associated with autoimmune oophoritis and ovarian tumorigenesis in neonatally thymectomized mice

Thymectomy at 3 days of age (Tx-3) in (C3H/HeMs x 129/J)F1 (C31) female mice results in post-pubertal ovarian dysgenesis associated with high levels of circulating auto-oocyte antibodies (AOA) prior to ovarian tumor formation. Evidence suggests that the etiology for the ovarian dysgenesis resulting from Tx-3 is autoimmune and involves helper T cell abnormalities. The present study characterized circulating leukocytes and mitogenic activity using concanavalin A (ConA) with serologically selected spleen T cells. We observed no sustained abnormalities in either number of circulating leukocytes or percentages of granulocytes or lymphocytes. Circulating mononuclear cells with positive immunofluorescence for Thy 1.2 and Lyt 1.1+Lyt 1.2 cell markers were similar in all mice. However, the spleen cells from Tx-3 mice with ovarian dysgenesis remaining after adsorption with antisera to the Lyt 2.1+Lyt 2.2 antigens (helper T cells remaining) showed increased incorporation of [3H]thymidine compared to the intact mice. This stimulated activity occurred during the periods of early ovarian dysgenesis and active tumor growth. Apparently, the autoimmune oophoritis results from an imbalance within the Lyt 1 cells which may represent a primary insult to the ovary that results in later ovarian tumor development.