Megavoltage pituitary irradiation in the management of prolactinomas: long-term follow-up

OBJECTIVE To determine the long-term effects of external beam megavoltage radiotherapy (RT: 4500 cGy via three portals at 180 cGy or less total daily dose) on endocrine function in prolactinomas. DESIGN Longitudinal study following radiotherapy with periodic re-assessment at regular intervals, at least 2 months off dopamine agonist therapy. PATIENTS Thirty-six female patients, age range 19-50 years, with either macroprolactinomas (12 patients) or microprolactinomas (24 patients), but without significant suprasellar extensions. MEASUREMENTS Clinical appraisal, and anterior and posterior pituitary assessment: basal levels at yearly intervals or less, with dynamic screening with TRH, LHRH and hypoglycaemic stimulation every 2-3 years. RESULTS Before RT, serum prolactin (PRL) levels ranged from 1150 to 34,000 mU/l; after RT (mean 8.5 years, range 3-14), serum PRL fell to normal (i.e. less than 360 mU/l) in 18 of the 36 patients (50%), and to just above the normal range (378-780 mU/l) in a further 10 (28%). Two patients had PRL levels at their last follow-up higher than those at presentation, with one patient showing evidence of tumour recurrence on CT scan. A total of eight of the 36 patients (23%) developed post-RT gonadal deficiency by the end of follow-up at 8 +/- 3.1 years (+/- SD, range 3-11), but six were aged over 40 years at that time. GH deficiency was frequent, occurring in 94% of patients, usually from 2 to 3 years post-RT, while TSH deficiency and reduced ACTH reserve was uncommon (each 14%), and occurred later. In the subgroup of 12 patients with macroprolactinomas, results were broadly comparable. CONCLUSIONS Megavoltage RT produces a progressive fall in serum prolactin in the great majority of patients with prolactinomas, with a relatively low incidence of TSH or ACTH deficiency. As it is now clear that dopamine agonist therapy alone provides sufficient management for microprolactinomas, RT may be used for the long-term control of macroprolactinomas, together with interim dopamine agonist therapy. It allows pregnancy to be safely undertaken but, in view of the delayed onset of gonadal deficiency, its administration should be timed with respect to the desired onset of conception in women.     

Low oxygen extraction fraction in tumours measured with the oxygen-15 steady state technique: effect of tissue heterogeneity.

Several reports have described decreased oxygen extraction fractions in tumours relative to those in normal tissues as measured with the oxygen-15 steady state technique and positron emission tomography. The present simulation study was carried out to assess the influence of tissue heterogeneity on these measured values. It was found that, within the range analyzed, tissue heterogeneity always resulted in underestimations of mean values of oxygen extraction fraction. It must, therefore, be concluded that the oxygen-15 steady state technique is not an accurate method for the assessment of the oxygen status of tumours. This finding should also apply to other pathological conditions, where a significant degree of tissue heterogeneity can not be excluded. More generally, this study demonstrates the need for detailed analyses of sensitivities of tracer kinetic procedures to tissue heterogeneity.     

Effects of cadaver dissection on the attitudes of medical students

Summary: Summary. A study was conducted to determine whether the attitudes of medical students to death and caring changed during the 3 months following exposure to cadaver dissection. All first-year students were invited to complete a questionnaire immediately before their initial cadaver dissection experience, after 6 weeks, and after a further 3 months. The questionnaire reflected attitudes to death, violent death, death of someone known to the respondent and caring when someone known to the respondent is seriously injured. Ethnicity and previous exposure to dying has no effect on responses, but overall men students' reactions were significantly less than for women ( P < 0.001). The responses given on the final part of the questionnaire after 3 months were significantly lower than those to most questions in the first part of the questionnaire. The exceptions were those questions where the subject in the given scenario was known to the respondent, where reactions were rated significantly greater ( P < 0.001) in the follow-up questionnaire and can be explained on the basis that they were a personal referent.
Students rapidly develop a coping mechanism which enables them to view cadaver dissection as an occupation quite divorced from living human beings. During these early months of training solicitude decreases for those who die who are unknown to them, but concern for personal referents increases. Educators should be aware of the dramatic change of attitudes among students and the process of professionalization which might influence their caring of future patients.     

Preoperative oral naproxen for pain relief after day-case laparoscopic sterilization

Analgesia with preoperative naproxen after laparoscopic sterilization was assessed in a prospective, double-blind, randomized study of 80 women; 42 women received oral naproxen 1 g, approximately 90 min before surgery, and 38 received placebo. Preoperative naproxen did not significantly influence postoperative pain scores, but was associated with a reduction in parenteral opioid administration (P = 0.04).      

Evaluation of the Usefulness of Open Lung Biopsies

The role of open lung biopsy (OLB) in the diagnosis of the etiology of lung infiltrates in children was analyzed for a 10-year period 1979-1989 in a tertiary referral center. A total of 18 children had 19 lung biopsies to ascertain the cause of lung infiltrates. Thirteen of these children (72 %) were immunocompromised due to treatment of hematological/solid malignancies and bone marrow transplantation. The clinical diagnosis was bilateral lung infiltrates of unknown etiology in 17 of 18 children. Eight of these children were ventilated for respiratory failure. The biopsy was useful in achieving a histological diagnosis in 18 of 19 samples (diagnostic yield 95%) and an etiological diagnosis in 14 of 19 samples (etiological yield 74 %). Therapeutic strategy was altered in 14 of 18 patients based on the biopsy results. Five of 14 patients responded favorably to a change in specific treatment. The lime interval from onset of respiratory illness to biopsy was 2-60 days (mean 16 days). Despite the critical state of these children there were few complications associated with the biopsy and no mortality directly related to the procedure. We recommend that OLE be undertaken sooner rather than later in immunocompromised children with bilateral pulmonary infiltrates of unknown etiology.     

A comparison of prospective and retrospective diary methods of assessing alcohol use among university undergraduates.

The objective of this study is to compare data about the quantity of alcohol consumed by university undergraduates using a prospective diary with those data collected using a retrospective diary. Five hundred and ninety-eight subjects were randomly selected and divided into two groups matched for age, sex, year of study and subject group; one group received a prospective and one a retrospective questionnaire-301 students received prospective and 297 retrospective questionnaires. Sixty-eight per cent responded to the prospective and 75 per cent to the retrospective survey. There was no significant difference in the median alcohol consumption detected for men or women in this study (p = 0.13; p = 0.47). However, the prospective diary recorded a greater proportion of heavy drinkers, this difference being significant for men and women (p less than 0.05). The quantitative results of the retrospective diary are similar to those obtained by a similar method in a previous survey. The conclusion is that a prospective diary detects a greater proportion of heavy drinkers than a retrospective diary. The prospective survey may be the most appropriate method for assessing alcohol use in certain situations.     

Cadmium Mobilization by Monoaralkyl- and Monoalkyl Esters of meso-2,3-Dimercaptosuccinic Acid and by a Dithiocarbamate

Syntheses and relative cadmium mobilizing properties are described for three new monoaralkyl esters (HOOCCH(SH)CH(SH)COOR, where R = phenylethyl ((CH₂)₂C₆H₅), MPhEDMS; R = 3-phenylpropyl ((CH₂)₃C₆H₅), MPhPDMS; and R = 2-phenoxyethyl ((CH₂)₂OC₆H₅), MPhOEDMS) of meso-2,3-dimercaptusuccinic acid. These were prepared by the reaction of the corresponding alcohol with meso-2,3-dimercaptosuccinic acid (DMSA) in aqueous HCl. When administered intraperitoneally to cadmium-loaded mice at 0.50 mmol/kg/day for four consecutive days, all induced significant reductions in the whole body cadmium levels. MPhEDMS, 60%; MPhPDMS, 66%; and MPhOEDMS, 58% in comparison with control levels. At the same dosage monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) and a dithiocarbamate, sodium N-benzyl-4-O-(β-D-galactopyranosyl)-d -glucamine-N-carbodithioate (BLDTC) induced reductions of 65% and 57%, respectively. Hepatic and renal cadmium were also depleted significantly, while brain cadmium levels were unchanged. These compounds induced a significant reduction in the cadmium levels of the spleen, and one, MPhOEDMS, produced a 10% decrease in pancreatic cadmium. The manner in which the later injections removed smaller fractions of the total body cadmium is consistent with a bodily distribution of these compounds by which they are concentrated primarily in the kidneys and the liver, with much smaller amounts reaching other organs. It is proposed that these compounds enter renal and hepatic cells through an anion transport system.