Appearance of Ph negative recipient clones in chronic myeloid leukemia patients following bone marrow transplantation.

Seven patients were studied following bone marrow transplantation for chronic myeloid leukemia. Cytogenetic heteromorphisms were used to determine the origin of cells present post-BMT. Differences were found between results from blood and bone marrow samples, and between karyotype and interphase Y-body studies on the same samples. Philadelphia negative (Ph-) hematopoietic chimerism was found in 6 of 7 patients, all of whom had been Ph+ before BMT. One patient also demonstrated hematopoietic chimerism with Ph+ recipient cells following clinical evidence of relapse. In two patients who had received T-cell depleted grafts, cytogenetically rearranged Ph- clones of recipient cells were prominent in PHA-stimulated blood. In one case two clones had appeared only 1 month post BMT. The appearance of these clones so soon after transplant suggests very rapid clonal expansion, or that they were already present pre-BMT but at levels too low to have been detected. In the second patient, clones were not observed until more than 12 months post-BMT, after which four were found. These collectively expanded to occupy an increasing proportion of the total cells. These two patients with clones both remain in good health 44 and 51 months post-BMT. Further studies are needed to determine the true frequency and the significance of such findings.

Development of a 12 element annular array transducer for realtime ultrasound imaging.

While the recent proliferation of ultrasound scanners based on annular array transducers has attracted widespread attention, very little published information is available on the physics, design criteria, and signal processing aspects of these instruments. In this paper, the first of a two part report, we describe the development and characterization of an annular array transducer for realtime medical imaging. Theoretical modeling of the pulsed fields of annular arrays is used to study and optimize array parameters. The factors which affect resolution and contrast in imaging--beam width, sidelobe levels, number of annuli, depth of field, and delay quantization--are discussed. A 12 element, 4.5 MHz, 30 mm design is adopted. Theoretical predictions showed excellent agreement with device measurements over a range of f-numbers (local/length/diameter) from f/1 to f/6.7 (30 to 200 mm range). Focusing to f/1 is an important advance in the state-of-the-art. A two transmit zone, dynamic receive configuration of array operation to exploit the f/1 focusing ability is proposed for realtime imaging.

A randomized trial of progestogens in the primary treatment of endometrial carcinoma.

A randomized trial was arranged in Yorkshire to assess whether progestogens would improve survival as part of the primary treatment of endometrial carcinoma, in conjunction with surgery and radiotherapy. A total of 429 patients was randomized on diagnosis to the progestogen or control group and treated locally according to an agreed protocol. All the patients are now more than 1 year after operation and over half are more than 5 years after operation. The projected overall 5-year survival rate is 76% but contrary to expectation there is no statistically significant difference in survival between the patients treated with progestogens and the control group even after statistical adjustment for known prognostic factors.

Extra-urethral ectopic prostate.

Extra-urethral ectopic prostatic tissue is a distinct entity which has been identified in the bladder of seven patients and may be more common than previously thought. Such tissue probably derives from the subtrigonal glands of Lowsley.

Endoscopic needle aspiration cytology: a new method for the diagnosis of upper gastrointestinal cancer.

A technique for obtaining needle aspiration cytology specimens from upper gastrointestinal lesions at endoscopy is described. The validity of the technique was initially confirmed by applying it to resected gastric carcinomas. Thirty seven endoscopically visualised lesions were then sampled by forceps biopsy, brush and needle cytology. Ten lesions were subsequently found to be carcinomas. Needle aspiration produced identifiable malignant cells from seven of these lesions. In two it was the only sampling method which provided the correct diagnosis. This technique may be a useful addition to conventional endoscopic sampling methods, particularly where tumours lie deep to normal mucosa, or necrotic slough.

Transabdominal chorion villus biopsy: 100 consecutive cases.

A series of 100 transabdominal chorionic villus biopsies were carried out for maternal age (34 patients), fetal sexing (15), previous aneuploidy (21), biochemical analysis (5), gene-probe analysis (17), and oligohydramnios or fetal anomaly (6). 18 patients were over 14 weeks pregnant at the time of sampling. Tissue samples were obtained from 98 patients, including one set of twins. All 99 tissue samples proved adequate for laboratory diagnosis. Chromosome mosaicism was encountered in 4 cases (among direct preparation karyotypes in 1 case, between direct and cultured cells in 2 cases, and between chorion cells [both direct and cultured] and the fetus in 1 case). No patient miscarried but 1 had a stillbirth and 1, who had undergone transcervical biopsy before referral to our hospital, started to bleed before termination of pregnancy because of a diagnosis of cystic fibrosis. These data suggest that the transabdominal method of chorion biopsy will fulfil its theoretical and early promise.

Outcome of carcinoma in situ and early invasive carcinoma of the bronchus.

Seventeen patients in whom a squamous carcinoma in situ of the bronchus had been resected have been followed for up to 16 years. The crude mortality rate for these patients is remarkably high, with seven (41%) dead after five years and 14 (82%) after 10 years. Half the patients had died as a direct result of malignant disease by 10 years--because of recurrence, metastatic disease, or the development of a second tumour. A guarded long-term prognosis must be given in these patients owing to the many deaths (mainly from other respiratory diseases) besides those from recurrent cancer.

Down's/Turner's mosaicism. Double aneuploidy as a rare cause of missed prenatal diagnosis of chromosomal abnormality.

Two babies with Down's/Turner's mosaic karyotype are reported. In each, because of advanced maternal age, chromosomal analysis had been carried out on the fluid obtained by amniocentesis in early pregnancy. Only the 46,X+ 21 cell line grew in the specimens and the extra 21 chromosome was wrongly identified as a Y chromosome, so that the fetus was thought to have a normal male karyotype, 46,XY. At birth both babies were phenotypically female with features predominantly of Down's syndrome and the correct karyotype was then identified. Twenty cases of this rare chromosomal abnormality are reviewed and one other living child who had been similarly wrongly diagnosed is reported.

Small-bowel mucosa in asymptomatic children with celiac disease. Mucosal changes with gluten-free diets.

Even though children with celiac disease may appear to be progressing satisfactorily while taking gluten-free diets, dietary lapses and persisting mucosal abnormalities are common. Of 32 children with celiac disease proven by biopsy only ten kept regularly to their diet, and 11 continued to ingest gluten regularly. Despite satisfactory clinical progress, intestinal biopsy specimens obtained after at least one year of a gluten-free diet were markedly abnormal in eight and were normal in only 14 children. Laboratory criteria also failed to detect those with persisting mucosal abnormalities. The only way to ensure that the small-bowel mucosa returns to normal and remains so is by intestinal biopsy.

Lung cancer, immune status, histopathology and smoking. Is oat cell carcinoma lymphodependent?

Life table analysis and partial correlation analysis have been used to examine the importance and interaction of those factors reported to affect prognosis in lung cancer, in a group of men taking part in a recent trial (Anthony et al. 1978). In patients with squamous carcinoma the lymphocyte count at diagnosis was a genuine correlate of survival, those with higher counts living longer. Patients who had smoked more heavily were younger when their tumours were found, had better differentiated carcinomas and longer survival. Those with poorer differentiation had weaker skin test reactivity but the expected shorter survival was seen only when controls for symptom pattern history and resectability were applied. These data could be explained by control of tumour extension by cell-mediated immunity, earlier induction of better differentiated tumours in heavier smokers, more insidious onset of symptoms in those with better differentiated tumours and the depression of cell-mediated immunity by poorly differentiated tumours. In contrast, the longer survivors among patients with oat cell carcinoma had lower lymphocyte and monocyte counts at the time of diagnosis. Lymphocyte and monocyte counts contributed independently to survival in keeping with oat cell carcinoma being lymphodependent (Prehn 1977) and resistant to immune cytolysis.

Cancer of the prostate: early diagnosis by zinc and hormone analysis?

Zinc, testosterone and dihydrotestosterone concentrations have been measured in normal prostatic tissue and in specimens obtained from untreated patients with benign prostatic hyperplasia (BPH) and carcinoma of the prostate (CaP). The metal--androgen relationship was examined and related to the pathological condition of the patients. The evidence suggests that discriminant analysis combining the hormonal data into a single variable is a reliable test for distinguishing between BPH and CaP patients. We have observed that the high Zn values found in BPH specimens were always associated with a DTH:T ratio greater than 1. Androgen tissue ratios less than 1 were characteristic of all CaP specimens, and these were usually preceded by a reduction in prostatic Zn concentration. Since these patterns, particularly those associated with neoplasia, precede the clinical manifestations, they may be used as an index for predicting the onset of carcinoma in the prostate gland. They may also be of value in monitoring the progress of the disease.

Levamisole and surgery in bronchial carcinoma patients: increase in deaths from cardiorespiratory failure.

Life table analysis of early entry to this randomised blind trial of 318 patients has shown a significantly poorer survival for resected lung cancer patients treated with levamisole for three days before operation and three days a fortnight thereafter than for placebo-treated controls. This excess was largely due to deaths that had been attributed to operation or other causes (non-cancer deaths), most occurring in the six weeks after operation. In the 99 resected patients treated with levamisole there was a 15% excess of deaths in this category, compared with the placebo-treated controls. Extensive analysis excluded maldistribution of patients between the groups as a cause of this difference. Many more died in respiratory distress, mostly without clear cause, in the levamisole group. Antibody (lgG) reacting with myocardial sarcolemma or sarcoplasm was found in the only serum samples available for testing which were drawn from patients during the syndrome. The findings are in keeping with a primary effect on the heart, possibly involving an autoimmune mechanism. The effect has not been noted in other trials.

A stratified randomized study of intradermal BCG in patients with carcinoma of the bronchus: prolongation of quality but not length of life in inoperable patients.

This paper reports the results of a stratified, randomized trial of monthly intradermal injections of Glaxo BCG in addition to conventional therapy (surgery, radiotherapy or no treatment) in a consecutive series of 75 men with confirmed bronchial carcinoma. BCG treatment did not significantly prolong survival but had consistenly more effect in prolonging the period in good general condition and in "acceptable" clinical condition. These were significantly prolonged among the BCG patients (all histopathologies) treated with a full course of radiotherapy (p = 0.01, p = 0.005) and among the 43 patients with squamous carcinoma after adjustment for treatment and general prognostic factors (ratio of observed to expected deaths (O/E) for BCG 0.65, P = 0.025). There was a tendency for BCG patients with oat cell carcinoma to survive less well than controls (O/E for BCG 1.40 not significant). Within comparable groups of patients with squamous carcinoma the delay in decline of general condition was accompanied by reduced weight loss.

Chromosomal abnormality in congenital rubella.

An infant with congenital rubella was found to have two extra chromosome fragements in most cells examined. This is an unusual finding in congenital rubella and it is suggested that it may be related to the infection.

Metal-androgen interrelationships in carcinoma and hyperplasia of the human prostate.

Zinc and cadmium concentrations were measured by atomic absorption spectroscopy in normal and pathological human prostates. Our studies confirm the values of zinc in normal tissue [6.84 +/- 1.21 (S.E.M.) mumol/g] and benign prostatic hypertrophy (BPH) (6.9 +/- 1.19 mumol/g) are similar, while in neoplastic tissues zinc concentrations were significantly lower (2.61 +/- 0.45 mumol/g). The Cd2+ levels in BPH (23.11 +/- 3.28 nmol/g) were, on the other hand, considerably higher than those found for normal tissues (5.15 +/- 0.62 nmol/g). In agreement with other published reports, Cd2+ concentrations were found to be markedly increased in carcinomatous tissue (129.79 +/- 22.22 nmol/g). No correlation was however established between the values for the two metals in either type of prostatic tissue. An established specific radioimmunoassay was used for the measurement of testosterone and dihydrotestoesterone (DHT) and a distinct pattern emerged upon comparing these results with those for the zinc and cadmium concentrations. It appears that the concentrations of DHT in benign hypertrophy and of testosterone and DHT in carcinoma were inversely proportional to the levels of Zn2+ in abnormal tissue. In contrast, the DHT levels in the hypertrophied and malignant tissue were proportional to the Cd2+ concentrations.

Biochemical assay by immobilized enzymes and a mass spectrometer.

By counting the volatile molecules produced by an immobilized-enzyme catalyzed reaction which is interfaced to a mass spectrometer via a semi-permeable membrane, a general approach to biochemical measurement and detection is obtained which offers the potential of high sensitivity, specificity and speed. In combination with molecule microscopy, this method should allow, for example, a mapping of suitable enzyme distributions in non-stained and non-fixed tissue slices. Immobilized urease (urea amidohyrdrolase, EC 3.5.1.5) was used to assay urea using CO2 as the volatile product, and alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) was used to assay NADH using ethanol as the volatile product.

A case of partial (9p) trisomy in a family with a balanced translocation 46,XX,t(1p+9q-).

A case of partial trisomy 9 is described, conforming that this will produce a recognizable syndrome of a characteristic facies with deep-set eyes and an unusual shape of the nose. Failure of secondary sexual characteristics to develop appears to be a feature in adults. In this case the mother had a balanced translocation between chromosomes 1 and 9 and must have, in addition, had a non-disjunction of her normal and her deleted No. 9 in order to produce the unbalanced state in her daughter.

E and EAC rosetting lymphocytes in patients with carcinoma of bronchus I. Some parameters of the test and of its prognostic significance.

Using peripheral blood lymphocytes separated by a Ficoll method and suspended in saline, means of 77-1% (s.d. 5-2) E rosettes (T lymphocytes) and 20-1% (s.d. 6-7) EAC rosettes (B lymphocytes) have been obtained with normal healthy donors. Poorer E-rosette formation resulted from higher centrifugation speeds during the washing of lymphocytes or erythrocytes, insufficient chilling, or rough handling. The presence of 5% albumin in the final mixture stabilized the rosettes and brought a constant subpopulation of B lymphocytes into rosetting. In patients with bronchial carcinoma who, at the time of diagnosis, had E-rosette percentages below 1 s.d. of the mean for normal donors, the length of survival was significantly shorter than in those with normal or high values. The same was true for those in whom null cells were detected. In each case the correlation effect was mainly found in the group of patients with squamous carcinoma.

E and EAC rosetting lymphocytes in patients with carcinoma of bronchus. II. A sequential study of thirty patients: effect of BCG.

T and B lymphocytes have been estimated in thirty patients with carcinoma of bronchus at monthly intervals. The patients have been treated by surgery, radiotherapy or no conventional antineoplastic therapy, with or without monthly intradermal BCG. Significant increase in T-lymphocyte percentages occurred in three out of six patients treated by BCG and no conventional therapy, and similar increases were observed in other BCG-treated patients. Patterns emerged suggesting that the T-lymphocyte percentage may be depressed, directly or indirectly, by tumour and recover after surgery or palliative radiotherapy; that high T-lymphocyte levels may accompany reactive lymphocytosis to tumour and that T-lymphocyte collapse was associated with, and appeared to precede terminal clinical deterioration in many patients.