Peter Rubin

Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity

On analysis ofin vitro assays of human natural killer (NK) cell function the inadequacy of commonly used methods of expressing lytic activity was apparent. A comparison was made of the data obtained using modifications of two equations—the simple exponential fit and the von Krogh equations. Both of these equations were found to satisfy the following essential criteria for use in these assays. First, the majority of the results obtained in the chromium-release assay could be used in data reduction; second, the resultant “dose-response” curve was reduced to linearity; and third, a single numerical expression was obtained which was directly proportional to the cytotoxic activity. Of the two methods the more conventional exponential fit was found to be the simpler to use. The closeness of fit of the experimentally derived data to the ideal curves did not support the possibility that normal lymphocyte preparations contain suppressor cells capable of inhibiting NK activity. Data have also been presented showing that NK-sensitive targets could be categorized with respect to their susceptibility by comparing the slopes of the target cell survival curves obtained using the exponential fit equation. These observations are relevant to the accurate assessment of NK activity in patient populations and to the determination of the effects of disease and its treatment on this activity.

Atenolol in essential hypertension during pregnancy.

OBJECTIVE--To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension. DESIGN--Prospective, randomised, double blind, placebo controlled study. SETTING--Hospital clinic. PATIENTS--33 Women with mild essential hypertension (systolic blood pressure 140-170 mm Hg or diastolic pressure 90-110 mm Hg on two occasions at least 24 hours apart) consecutively referred to two obstetric medical clinics. Four patients in the placebo group were withdrawn from the study: control of blood pressure was inadequate in two, one developed breathlessness, and one changed her mind about participating. The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks. MAIN OUTCOME MEASURES--Blood pressure and birth weight. INTERVENTION--14 Women received placebo. 15 Women received atenolol 50 mg daily initially, increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached. RESULTS--The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo. During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo (to 74 v 81 mm Hg; difference in means (95% confidence interval) 7.0 (2.9 to 10.0) mm Hg) but the effect on systolic pressure was marginal (132 v 136 mm Hg; 4.0 (-1.4 to 8.6) mm Hg). Babies in the atenolol group had a significantly lower birth weight than those in the placebo group (2620 g v 3530 g; 910 (440 to 1380)g). CONCLUSION--Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation. When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy.

Prospective survey of use of therapeutic drugs, alcohol, and cigarettes during pregnancy.

Use of drugs during pregnancy was recorded prospectively in 2765 women attending the antenatal clinics of a general hospital from October 1982 to March 1984. Of these women, 2588 (93.6%) avoided exposure to drugs during the first trimester, 1802 (65.2%) took no drugs at any stage, 963 (34.8%) took a total of 154 different drugs from 35 groups of drugs, and 243 (8.8%) took a self administered drug. The most commonly used drugs were non-narcotic analgesics, usually self administered, and antibacterials. The last survey of use of drugs in pregnancy in the United Kingdom 20 years ago showed fewer women avoiding drugs throughout pregnancy (195 of 911 (21.4%), p less than 0.001) and in taking a self administered drug (586 (64.4%), p less than 0.001) than at present. Most women nowadays abstain totally from alcohol (1786 (64.6%) v 109 (12.0%) previously, p less than 0.001), but while more women are non-smokers compared with previously (1811 (65.5%) v 392 (43%), p less than 0.001) the trend has been far less dramatic than that for use of alcohol.

Tumor cell differentiation modulates susceptibility to natural killer cells

Abstract Induced differentiation in three human cell lines altered their sensitivity specifically to human natural killer (NK) cells by affecting their expression of NK target antigens. Differentiation of HL-60, a promyelocytic leukemia cell line, and the erythroleukemic cell line K562 was accompanied by a concomitant decrease in susceptibility to NK-mediated lysis whereas induction of MeWo melanoma cells resulted in an enhanced sensitivity to lysis. Our findings suggest that target cell susceptibility to NK-mediated lysis may in part be dependent on the stage of differentiation of the tumor cell target.

Measuring diastolic blood pressure in pregnancy

The measurement of diastolic blood pressure during pregnancy offers plenty of scope for error. Most people still use a mercury sphygmomanometer, with all the pitfalls that are familiar outside obstetrics–“white coat” hypertension, digit preference, cuff size, differences between arms, and poorly calibrated equipment. To these should be added the influence of posture and gestation in a pregnant woman, so any advance in getting it right is to be welcomed. There is now good evidence to support using the fifth Korotkoff sound when measuring diastolic blood pressure in pregnancy. Although measuring blood pressure and detecting hypertension remain at the core of antenatal monitoring, there has long been uncertainty about whether to record diastolic pressure as the point when the sounds muffle (Korotkoff phase IV) or when they disappear (phase V). The World Health Organisation recommends the use of phase IV,1 …

Magnetic resonance spectroscopy in pre-eclampsia: evidence of cerebral ischaemia

Objective To establish whether there are changes in the maternal brain in pre‐eclampsia detectable by magnetic resonance angiography and spectroscopy.

Studies of human natural killer cells. III. Neutropenia associated with unusual characteristics of antibody-dependent and natural killer cell-mediated cytotoxicity

A 52-year-old Caucasian man with chronic neutropenia and recurrent infections was found to have an increased proportion of peripheral T lymphocytes having Fc receptors for IgG (T(γ). Although levels of antibody-dependent cell-mediated cytotoxicity (ADCC) and “natural” killing (NK) by unfractionated lymphocytes were similar to those of a control donor, the frequency of NK cells was markedly increased. Removal of E rosette-forming cells eliminated both NK and ADCC by the patients peripheral blood, in marked contrast to theenhanced cytotoxicity seen with control lymphocytes. Both normal and patient ADCC and NK functions were removed by depletion of Fc receptor-bearing cells. These depletion experiments proved that all of the patients killer cells were E rosetteforming Tγ cells, in contrast to the heterogeneous pattern of Nullγ and Tγ killer cells seen in the blood of normal donors. The homogeneity of the Tγ proliferation suggested that ADCC and NK were mediated by the same cell type, albeit acting by different mechanisms. The addition of the patients serum and lymphocytes to chromiumlabeled normal granulocytes caused a low but significant level of cytotoxicity, indicating that the patients neutropenia may have been caused by a similar mechanismin vivo. There was no evidence of complement-dependent serum antibody-mediated neutrophil lysis, but one serum sample taken over the course of the patients disease agglutinated granulocytes from four of five donors tested.

Five times: coincidence or something more serious?What should a junior doctor have done?You cannot expect people to be heroesPut out the fire or risk an infernoPresent system of whistleblowing is unsatisfactory

# Five times: coincidence or something more serious? {#article-title-2} See Editors choice The anonymous article below was sent to us by a doctor outlining the concerns he had about the competence of a surgeon he once worked with when he was a junior doctor. We asked four other doctors what the junior should have done, what they would have done had they been approached by the junior, and what the implications are for the regulation of medicine. Perioperative mortality (death within 28 days of an operation) has became a key surgical phrase in the past decade, particularly after the publication of the first report of the confidential inquiry into perioperative deaths. This document detailed a variety of surgical and anaesthetic disasters, and, although it pointed out that many perioperative deaths were and remain unavoidable, there were contributory factors such as inadequate hospital facilities, poor supervision of junior doctors, and inappropriate surgery in severely ill patients. This and subsequent reports, together with regular intradepartmental and interdepartmental audits, have raised the awareness of perioperative mortality. All operative deaths should now be discussed to discover if care could have been improved or death avoided. I have been fortunate to be a surgical trainee in these more enlightened times. Usually, the audits I have attended have had an average of one death every six months from routine general surgery lists (somewhat more from emergency surgery), and even fewer during my five years in specialist training. With one exception: during a six month period on one firm, five patients on routine lists died from a variety of reasons. All of these patients were led to believe that their conditions would be substantially improved if not cured by the surgery, and yet within a matter of days they were dead. I felt at the time that certain questions were overlooked, if not ignored. My polite …

Not what we used to be

Did a golden age of medical education ever exist, asks Peter Rubin

How the General Medical Council’s national training survey helps improve medical education

Each year, the General Medical Council conducts its national training survey to monitor the quality of medical education and training, and the 2014 survey is now open. Peter Rubin, the council’s chairman, and Sonia Panchal, a specialist trainee, discuss how the survey is used to improve training, and the importance of using it to provide open and honest feedback