Immunological study of patients with Hodgkin's disease in long-lasting not-maintained complete remission. Immunological parameters have been evaluated both in vitro and in vivo in 20 Hodgkin's disease patients in continuous not maintained complete remission for at least 3 years. IgG, IgA and IgM levels were within the normal range. Delayed sensitivity, assayed by a battery of recall antigens, was normal too, in the majority of patients. The number of circulating lymphocytes was slightly inferior to normal controls. T cells, evaluated by the rosette E formation, seems to be diminished; on the contrary, B cells, evaluated by the membrane immunofluorescence, were increased in respect to normal controls. The differences are statistically significant. Timidine uptake of PHA stimulated lymphocytes was diminished too. It is concluded that even if these patients' clinical behaviour is like that of normal population, it is possible to find a disorder in vitro parameters, which could be attributable to long lasting effect of the therapy and/or to the persistence of serum factors acting as anti-T cells antibodies.


[The ELISA test in immunodiagnosis of human hydatidosis. Preliminary observations]. An evaluation of the E.L.I.S.A. method, compared to the indirect hemagglutination (I.H.) and to the counterimmunoelectrophoresis (CIEP) tests for the biological diagnosis of hydatidosis, was performed on 31 sera of patients, carrier of hydatid cysts, on 17 sera of patients with other infectious and parasitic diseases, and on 7 sera of blood donors. The immunoenzymatic test turned out positive in 30 out of the 31 sera of the patients with active hydatidosis (96.7%), while IH and CIEP turned out positive in 29 cases (93.5%). The control sera from patients with other diseases proved to be all negative, except one from a patient with active schistosomiasis. E.L.I.S.A. test was constantly negative with the sera of normal subjects. The validity and usefulness of E.L.I.S.A test for the diagnosis of the hydatid disease is discussed.


Intramuscular diazepam in labour. A double-blind trial in multiparae. Diazepam 0.2 mg/kg, diazepam 0.3 mg/kg or a placebo were administered i.m., during labour, in a double-blind fashion to 28 multiparous patients. Although there were no significant differences in the requirements for i.m. pethidine during labour, diazepam was associated with a superior quality of pain relief. Diazepam 0.3 mg/kg i.m. produced no obvious adverse effects upon the neonate.


Influence of milk source on transplantability of histocompatible mammary tumours in mice. It is confirmed that C3H mammary tumours are much more easily transplantable in histocompatible recipients when these have been reared on C3H milk, than when they have been reared on milk from the inbred Swiss/B strain. By contrast, A.CA mammary tumours transplanted in histocompatible hosts reared on A.CA or Swiss/B milk, grow almost equally well in both sorts of recipient. Thus, rearing on Swiss/B milk has different effects on the transplantability of mammary tumours of C3H and A.CA. On the other hand, recipients which were reared on C3H or A.CA milks accept grafts of C3H mammary tumours about equally, suggesting that milks from A.CA and C3H have the same effect on the transplantability of C3H mammary tumours. The different action of Swiss/B milk on tumours of C3H and A.CA seems best attributed to differences between C3H and A.CA tumours or between mouse strain genotypes. By contrast, the transplantability of C3H mammary tumours is significantly changed when the recipients were reared on milk from the RIII strain instead of C3H. These facts suggest that the milk from RIII has an action which differs from that of both C3H and A.CA in this respect. The data are discussed on the basis of a differential tollerance-inducing action of mammary tumour viruses (MTVs) which infect C3H, A.CA and RIII, and have an important role in tumour induction.


Increased expression of actin-like contractile protein in preneoplastic and neoplastic lesions in rat liver. Cryostat sections of 16 preneoplastic and 14 neoplastic hepatic lesions induced in rats by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) were examined by indirect immunofluorescence with human serum containing smooth-muscle antibody (SMA). Preneoplastic lesions showed strong cytoplasmic staining of proliferating oval cells and of the cell outlines of hepatocytes, in areas of nodular hyperplasia. In carcinomas, poorly differentiated hepatocytes showed staining of cell outlines, while well differentiated tumour cells forming glandular structures showed only staining of the luminar surfaces. The stromal cells also showed cytoplasmic staining. Morphologically normal areas of 3'-Me-DAB-treated livers showed weak staining of cell outlines, similar to normal liver. Specificity of the staining reactions was established by failure of staining in parallel control sections treated with normal human serum, or SMA serum neutralized by absorptions with homogenates of smooth muscle or extracts of actin. The results suggest that there is an increased expression of actin-like contractile protein in preneoplastic and poorly differentiated neoplastic liver cells.


Measurement of liver blood flow in the rat using an 85Krypton clearance technique. A method for the measurement of liver blood flow (LBF) in rats has been developed by recording the clearance of 85Kr from the liver after injection of a solution of the gas into the portal vein. This technique provides a measure of tissue perfusion at a cellular level. The animal preparation was maintained in a stable haemodynamic and respiratory state for up to 4-3 h by careful fluid and anaesthetic control. Stability of the model was reflected by relative constancy of the LBF measured throughout the experiment in all of the animals studied. The mean LBF determined in six rats was 2-41+/-(s.d.) 0-50 ml/g/min.


Liver tissue blood flow measured by 85Kr clearance in the anaesthetized rat before and after partial hepatectomy. The changes in liver haemodynamics following partial hepatectomy (PH) were studied using an 85Kr clearance technique to measure perfusion in the livers of rats before and after both PH and sham operations. Post-operative measurements were made for 8 h following operation and also at 21 and 35 h, when uptake of tritiated thymidine into DNA is maximal in regenerating rat liver. Sham operation did not influence hepatic perfusion, arterial pressure or portal pressure. PH induced an early increase in perfusion of 293% in spite of a decrease in arterial blood pressure during the initial 4 h. The increase in perfusion lasted at least 8 h, had returned to normal values by 35 h, and was not explained solely by an observed elevation of portal pressure of 50% which returned to normal 5 h postoperatively. The total volume flow to the liver remnant after PH, however, was essentially the same as the flow to the liver before operation.


Enteric flora of normal laboratory guinea-pigs. The bowel flora of guinea-pigs was studied using non-selective cultural conditions and conditions highly selective for Escherichia coli organisma. No E. coli were cultured from adult or juvenile bowel content. Parallel studies showed that culture media supported the growth of small numbers of reference E. coli "seeded" into them along with bowel content. It is concluded that normal adult laboratory guinea-pigs may be bacteriologically equivalent to the NCS strain of "E. coli-free" mice.


The isolation and characterization of a bile ductule cell population from normal and bile-duct ligated rat livers. The separation of bile ductule cells from Kupffer and sinusoidal endothelial cells in a suspension of non-parenchymal cells has been attempted. Bile duct ligation was performed so that a four-fold increase in the total number of non-parenchymal cells isolated from rat liver was attained and the proportions of both Kupffer and bile ductule cells were elevated. Rate zonal centrifugation, through a Ficoll gradient, partially separated the cells into two populations: (1) small cells (4-6 micrometer diameter) probably originating from the sinusoidal endothelium and (2) larger bile ductule and Kupffer cells (8-12 micrometer diameter). A more successful separation was achieved by isopycnic centrifugation through a linear metrizamide gradient. Bile duct ligation (14 days) altered the distribution of cells on the gradient and the peak containing bile ductule and Kupffer cells partially subdivided into the separate cell types. Antiserum raised against the bile ductule fraction was shown to be compatible with that raised against common bile duct tissue. gamma-glutamyl transpeptidase and leucine aminopeptidase activity were preferentially located in the rate zonal fraction containing bile ductule cells. Their specific activity increased after bile duct ligation as did that of beta-glucuronidase, which was raised in all cells.


Dermatitis herpetiformis and reticulum cell sarcoma, a rare complication. A patient with longstanding dermatitis herpetiformis and adult coeliac disease developed perforation of a jejunal reticulum cell sarcoma. This is probably the third reported case of reticulum cell sarcoma occurring in association with dermatitis herpetiformis.


Herpes gestationis. A high titre of anti-HLA-B8 antibody in the mother and pemphigoid-like immunohistological findings in the mother and the child. A mother with herpes gestationis and her child without cutaneous lesions had analogous immunohistological findings. In the skin they had deposits of IgG and C3 component of complement at the basement membrane zone. Circulating IgG antibody to the basement membrane was also demonstrated in both. The mother also had a high titre of anti-HLA antibody against a histocompatibility antigen (HLA-B8) present in the child. A possible role of this HLA antibody in the pathomechanism of herpes gestationis is discussed.


Cytoplasmic and HL-A antigens in the human epidermis. HL-A antisera were found to react, in indirect immunofluorescence on human skin, with the cytoplasm of the upper cell layers of the epidermis. It has been established that this staining was not due to an HL-A-antigen-antibody reaction but rather to a contamination of HL-A antisera with non-HL-A epidermal cytoplasmic antibodies. These findings ruled out a previous hypothesis that HL-A antigens were expressed in the cytoplasm of the upper epidermal cell layers. The localization of HL-A antigens in the human epidermis has not been demonstrated by use of indirect immunofluorescence.


Betamethasone valerate aerosol in the treatment of oral lichen planus. Betamethasone valerate aerosol, given in doses of up to 800 microgram per day, was compared with placebo in a double-blind trial involving 23 patients with oral lichen planus. The majority of patients receiving the active aerosol noted improvement within the first 2 weeks of treatment and at 8 weeks the lesions had almost cleared; in contrast, only 2 patients on placebo showed slight improvement over the same time period. The results suggest that this form of treatment is an effective and acceptable method of controlling the discomfort due to oral lichen planus, especially where minor erosions are present.


The measurement of granulocyte kinetics. Studies using 3H-TdR, DF32P or 51Cr have all contributed important information concerning neutrophil kinetics in normal and abnormal conditions. Recent evidence, however, suggests that DF32P underestimates, and 51Cr overestimates, the blood neutrophil T1/2 and that both isotopes overestimate the TBNP, compared with 3H-TdR-derived data. The differences are quantitative and not qualitative, and the principles of blood neutrophil kinetics defined by DF32P studies are still valid. 3H-TdR studies are impractical for general use, and clinical measurement of neutrophil kinetics will have to continue to rely on the use of either DF32P or 51Cr. Comparison of abnormal findings with normal values obtained using the same isotope is probably valid for either technique. Changes in neutrophil kinetics leading to a neutrophil leucocytosis in different situations are fairly predictable from published data. In neutropenias, however, kinetic studies might be needed to delineate the relative contributions of under-production, shortened survival and excessive margination in the individual patient.


Inhibition of leukaemia blast cell motility as a test for specific antibody in acute adult myelogenous leukaemia. Migration studies of acute myelogenous leukaemia blast cells in autologous diagnostic and remission sera from a series of 11 patients have demonstrated two factors. A factor of less than 70 000 molecular weight appears to potentiate blast cell migration whereas the other of molecular weights 100 000-250 000 inhibits blast cell migration relative to a standard non-immune AB serum. The low molecular weight fraction was found in the serum of patients prior to relapse while the greater molecular weight fraction was possibly an IgG antibody that increased in concentration with length of remission. The inhibitory factor was found in patients following immunotherapy and in one patient who received chemotherapy alone. An inhibitory factor was also consistently found in patients in overt clinical relapse following on remission induction and maintenance therapy.


Effect of topical atenolol on intraocular pressure. Placebo and topical atenolol (Tenormin), a selective beta1-adrenergic blocking substance with no intrinsic sympathomimetic or membrane-stabilising properties, were tested in 16 patients with ocular hypertension in a double-blind cross-over trial. Three different concentrations of atenolol (1, 2, and 4%) were investigated. After a single instillation there was a statistically significant fall in mean intraocular pressure (IOP) with all the concentrations after one hour, with a maximum after two to three hours. The effect had passed off after seven hours. In multiple-dose studies with applications three times a day for seven days there was a statistically significant fall in the mean IOP on the first day of treatment (all three concentrations), which persisted throughout the week. In the single-dose study only a slight dose-dependence was observed. This could not be confirmed in the multiple-dose trial. Pupil size, corneal sensitivity, systemic blood pressure, and heart rate were unaffected. No side effects were noted. Thus topically applied atenolol lowers IOP in patients with ocular hypertension and may be clinically useful.


Comparison of ocular hypotensive effects of acetazolamide and atenolol. The ocular hypotensive effect of single oral doses of (a) atenolol (50 mg), (b) acetazolamide (500 mg), (c) atenolol (50 mg) and acetazolamide (500 mg) in combination, and (d) vehicle (inert tablets) were compared in 8 patients with glaucoma. In this single-dose, double-masked trial the combination was observed as most effective in reducing ocular tension. Both the combination and atenolol performed markedly better than vehicle. That acetazolamide did not reduce ocular tension significantly more than vehicle is probably explained by relatively low initial ocular tensions. There was no evidence of interaction between atenolol and acetazolamide in this study. Acetazolamide probably remains the first-choice oral medication for glaucoma. It is cautiously suggested that beta-blocking drugs may have a future therapeutic role, but longer-term studies on larger numbers will be required to establish this.


Atenolol eye drops in glaucoma: a double-masked, controlled study. Guttae atenolol 4% (Tenormin), a pure beta1-blocking (i.e., cardioselective) drug, produced a median overall fall of 5-6 mmHg (range 3-2 to 13-2 mmHg) in the first tonometrised eyes of 7 patients with open-angle glaucoma or ocular hypertension and 1 with closed-angle glaucoma (off any treatment for the whole of the day preceding each test day) after allowance for an 'effect' of guttae saline 0-9%, in a double-masked, cross-over trial. By a Wilcoxon matched pairs rank test this was significant at the P less than 0-05 level. The median overall fall of 3-5 mmHg (range 0-8 to 10-8 mmHg) in the second-tonometrised eyes of 7 patients (1 of the 8 contributed only 1 eye) was also significant (P less than 0-05). In 2 patients who had been treated with guttae atenolol 4% daily 3 X for 1 and 2 months there is evidence that, on replacing the atenolol 4% with saline 0-9%, a rise of pressure of around 3 mmHg occurred 2 and 3 and 5 days later, i.e., the drug still retained its effectivity (slightly reduced) after 1 and 2 months.


Astigmatism in cataract surgery.

Astigmatism in cataract surgery. We report on our investigation into astigmatism in 40 eyes following a corneal cataract incision closed with a continuous 10/0 nylon monofilament suture (Ethilon). Immediately after surgery there was astigmatism caused by the nylon suture (suture-induced astigmatism), its severity depending on the tightness of the suture. It ranged from 1 to 10-5 dioptres, the mean value 4-09 dioptres with a standard deviation of +/-2-5. Removing the nylon suture eliminated this astigmatism and within a few weeks the corneal astigmatism correction in 48% of eyes returned to the preoperative level. In 80% of eyes the difference between the final postoperative corneal astigmatism (4 months after removing the continuous suture) and the preoperative astigmatism was 0-75 dioptres or less and the maximum change was 1-5 dioptres. In 40% of eyes the axis of the cylinder changed from a horizontal to an oblique axis but did not change from a with- to against-the-rule axis. The degree of astigmatism remained constant while the suture was in place and in 50% of eyes was equal to or less than 3 dioptres. The mean of the spherical equivalents was 11-31 dioptres with a standard deviation of +/-1-25. A spectacle correction 14 days after operation prescribed either as the mean spherical equivalent (11-50 dioptres) or according to the patient's refraction will give satisfactory vision until the suture is removed 4 months after operation. The degree of astigmatism following a corneal section and continuous nylon suture compares very favourably with astigmatism following other suturing techniques for cataract.


Immunopathology of the lens. III. Humoral and cellular immune responses to autologous lens antigens and their roles in ocular inflammation. In experimental rabbits it has been shown for the first time that autologous lens protein is antigenic when injected with Freund's complete adjuvant. Although lens haemagglutinins were detected in 6 out of 7 rabbits, in only 3 of the 6 animals did the titre reach a maximum of 1:640. A weak agar precipitation reaction was obtained with only 1 of the 3 sera. It would appear, therefore, that the passive haemagglutination test is superior for the detection of autologous lens antibodies. The response to autologous lens antigen both in magnitude as well as in duration varied in different rabbits, which suggested to us the possible role played by a central control mechanism involving the immune-response (Ir) and immune-associated (Ia) genes which are part of the major histocompatibility complex. Alternatively, this variation may be the result of an antigenic competition between various autologous crystallins. Antibodies to autologous lens protein as detected by immunofluorescence and immunoperoxidase techniques were shown to be of the IgG class. Systemic autologous immunisation produces only a mild uveitis and does not lead to a granulomatous intraocular inflammation. Intravitreal injections of autologous lens protein in pre-immunised animals, however, produced an Arthus type of acute endophthalmitis. Autologous lens antisera showed limited cross-reactivity with ocular and extraocular tissues, which could be detected only by such sensitive techniques as immunofluorescence and immunoperoxidase methods.


Treatment of early diabetic retinopathy with cyclandelate. In order to assess the effect of cyclandelate on the abnormal permeability of the blood-retinal barrier which occurs in diabetic patients before any other lesions are apparent in the retina a well-controlled, double blind, and paired trial was carried out in 22 patients. The treatments were randomised. The permeability of the blood-retinal barrier was assessed by vitreous fluorophotometry. Each patient was examined before being involved in the trial and then another 3 times with 1 month's interval. The total duration of treatment was 3 months. The results showed that the breakdown of the blood-retinal barrier as evidenced by the degree of abnormal fluorescein penetration into the vitreous suffered a significant decrease in the diabetic patients treated with cyclandelate when compared to the patients submitted to placebo administration, and this effect is particularly apparent in the third month of treatment.


Cryptococcal chorioretinitis: a case report. Chorioretinitis occurred in a young man whose long-standing cryptococcal meningitis had been identified and treated. In one eye spontaneous resolution had occurred. His case history and fluorescein angiograms are presented.


Follow-up of stereotaxic amygdalotomy for seizure and behavior disorders. Stereotaxic amygdalotomy for the control of unmanageable behavior and/or intractable seizures is a controversial treatment approach with unknown risk-to-benefit ratios. Information about this subject was obtained from a retrospective follow-up study of 58 patients who received this form of treatment 1 to 11 years earlier (average 6 years). Assessments of the patients were made by invesgators external to the surgical treatment system, using structured psychiatric interviews, neuropsychological tests, and EEGs. In addition, global assessments were made, comparing pre- versus postoperative status. The objective data revealed no indication of worsening or damage with similar pre- and postoperative test scores and EEG features. Computer-scored interviews revealed considerable psychopathology in the ambulatory patients. Overall judgments of behavior, seizures, and functional levels indicated that more than a third of the group was probably improved, although the relationship of outcome to the surgery was indeterminate.


Preparation of mononuclear cell subpopulations from normal human peripheral blood. By the use of velocity sedimentation at unit gravity, in combination with methods of cell separation based on differences in density and in surface membrane receptors, it has been possible to obtain concentrates of mononuclear cell subpopulations from normal human peripheral blood. T and non-T lymphocytes have been harvested with a good yield and a high degree of purity. Monocytes may also be efficiently recovered using these procedures.


Quantitative study of T and B lymphocytes in Hodgkin's disease. Peripheral  blood lymphocytes forming E rosettes in the presence of sheep red blood cells and those bearing surface immunoglobulins (SIg) have been studied quantitatively as an evaluation of T and B lymphocytes in Hodgkin's disease. 62 patients were investigated, 21 of whom before any treatment. It appears that the lymphocytes forming E rosettes are significantly lower in percentage in 86% of the patients and in absolute count in 65%. SIg bearing lymphocytes are elevated in percentile in 61% of the cases, but the absolute count is normal in 50% of the patients and elevated in 30% only. At diagnosis the T/B lymphocytes equilibrium is modified in 13 among 21 patients but, after the initial treatment of the disease, the ratio is modified in 90% of the patients in complete remission and remains unchanged for years even in the absence of relapse or immnunosuppressive treatment. It is suggested that SIg + lymphocytes from the peripheral blood are actually B lymphocytes and not anti-T-antibody coated T lymphocytes or antigen-antibody lacking of membrane markers, which are numerous in one third of the investigated patients, might be T lymphocytes with qualitative abnormality.


Immunostimulation or immunodepression?

Immunostimulation or immunodepression? Our experimental studies and extensive literature survey established that the overall response of an experimentally modified host defense system is strongly dose-dependent, irrespective of either the modifying agent or the test model system. If a sufficiently broad dose range is used, an irregular, nonlinear, nonmonotonic response curve is formed, generally W- or M-shaped, depending on the parameters selected for the representation, with two peaks of relative maximal effect. Accordingly, a modifying agent may exhibit, in some cases, dual effect--stimulation and depression, each at different dose levels. This typical response is defined as characteristic of the entire host defense system and therefore implies a biologically integrated system. The described dose-response relationship mandates the use of multiple doses in evaluation experiments, to establish efficacy and especially to design optimal dose schedules for experimental and clinical application of any agent modifying the host defense system activity.


Effect of procaine HCLl on ATP: calcium-dependent alterations in red cell shape and deformability. Procaine hydrochloric acid, a cationic anesthetic, although unable to prevent the effect of calcium ionophore A23187 on erythrocytes, inhibited the discocyte--echinocyte transformation, increased viscosity, and decreased filterability of red cells undergoing ATP depletion. The effects were abolished by washing ATP-depleted, procaine HCl-treated red cells prior to these determinations. Procaine HCl had no effects on volume, incubated osmotic fragility, or monovalent cation composition of ATP-depleted red cells. The drug increased 45Ca uptake by ATP-depleted red cells but did not change the fraction of membrane-bound calcium. Sodium dodecyl sulfate acrylamide gel electrophoresis of membrane proteins from ATP-depleted red cells revealed formation of high molecular weight protein complexes, which were not formed when biconcave shape and ATP content were maintained by incubation with adenine (0.54 mM) and inosine (12.7 mM); Formation of these complexes was not prevented when the biconcave shape was maintained by procaine HCl. It was concluded that the maintenance of the biconcave shape and normal deformability during ATP depletion by procaine HCl was not related to a displacement of membrane-bound calcium and inhibition of ATP-dependent rearrangement of red cell membrane proteins.


ABO blood group system and bone marrow transplantation. The role of the ABO blood group system in determining the outcome of bone marrow transplantation was investigated in 53 patients with aplastic anemia and acute leukemia grafted from HLA-identical siblings. There was no correlation between ABO compatibility and marrow engraftment, graft rejection, or graft-versus-host disease. In 5 recipients with antibodies prior to transplantation to antigens of the ABH system present on the cells of their donors, plasma exchange and antibody absorption in vivo were effective in permitting engraftment of ABO-incompatible bone marrow. These findings indicate that the ABO system is not a clinically significant barrier to successful bone marrow transplantation in otherwise histocompatible individuals.


Slide chamber culture system for the in vitro study of humoral regulation of granulocyte and monocyte-macrophage proliferation and differentiation. A liquid culture system employing slide chambers was developed to facilitate the study of proliferation and differentiation of mouse neutrophilic granulocytes and cells of the monocyte-macrophage series. Cultures were initiated with 1-2.5 X 10(4) light density marrow cells which had been fractionated on Ficoll-Hypaque. In the presence of colony-stimulating activity (CSAHU), two types of clusters were observed. One was tight, spheroidal, and composed of neutrophilic granulocytes, while the other was a loose grouping of flattened cells of the monocyte-macrophage series. The slide chamber culture is adaptable to microscopic assay techniques (e.g., cluster size, autoradiography, immunofluorescence) as well as quantitative biochemical methods (e.g., rate of 3H-thymidine incorporation, DNA quantitation). We have demonstrated both a shortening of the generation time of granulocytes in tight clusters and increasing rates of 3H-thymidine incorporation into DNA, with a corresponding increase in total culture DNA as a function of CSAHU concentration. Granulocytic differentiation in the tight spheroidal clusters has been demonstrated by histochemical stains and immunofluorescence of an antibody to a marker protein specific for the secondary granule of the neutrophil (lactoferrin).


The management of urinary infections in children. Urinary tract infection is a common disorder of childhood which frequently causes no symptoms. Bacteriological proof should always be obtained because symptoms may be misleading. The diagnosis of a first infection should lead to radiological investigation. Routine tests to localize the site of infection are not yet available but their use in the future in conjunction with increased awareness of the factors leading to pyelonephritis should help to identify children at risk from renal damage. Two thirds of children with urinary infections have normal lower urinary tracts or only minor abnormalities and may be treated for symptomatic infections with intermittent antibiotics. The risk of renal damage from infection is virtually confined to the remainder: children with obstructive uropathy, preschool children with severe vesicoureteric reflux, and those with pre-existing chronic renal failure. It remains to be shown by controlled therapeutic trials whether renal scarring can be prevented by long-term chemoprophylaxis or surgical correction of reflux. Until the results of current trails are known, children with reflux or impaired renal function should be treated medically in the first instance and screening of healthy children for covert bacteriuria should probably be confined to the preschool age-group.


Children's perceptual organization of seriated displays: evidence against a memory reorganization hypothesis. The memory for a seriated display and its reorganization over an eight-month interval was examined in educationally subnormal children. By including groups of children who viewed a random display and an array of disordered sticks, it was found that the reorganization into a more seriated drawing after the passage of time was not directly based on the original stimulus. Various controls including copying of the original material, and matching and recognition conditions, give evidence that the child's cognitive level affects encoding of the material as well as its later output. The observed phenomenon of 'memory' improvement may have little to do with stored images, and may instead be linked to the developmental symbolic level of the child which influences original perception as well as 'memory'. It was also found that educationally subnormal children perform like normal children of the same mental age on the seriation task.


A comparison of piribedil, procyclidine and placebo in the control of phenothiazine-induced parkinsonism. A double-blind, cross-over trial of the effectiveness of piribedil, procyclidine and placebo in the control of parkinsonism induced by fluphenazine decanoate was conducted in sixteen cases of chronic schizophrenia. Procyclidine was shown to be more effective and piribedil less effective than the placebo. Piribedil produced a number of unpleasant effects, including headache, vomiting and malaise.


A prospective trial of prophylactic antibiotics in hand lacerations. A series of 368 patients with hand lacerations which required suturing were randomly allocated to one of three treatment groups. The incidence of infected and of imperfectly healed wounds was noted 7 days after suturing. As well as the influence of antibiotics on healing, sixteen other factors which it was considered might affect healing were analysed. The overall infection rate was 9-8 per cent, and there was no significant difference between the three groups. The imperfect healing rate (which includes the infected cases) was 24-6 per cent. There was a lower rate (P less than 0-05) of imperfect healing in the Triplopen group (15 per cent) than in either the flucloxacillin group (29-5 per cent) or the group who received no antibiotics (29-0 per cent). Other factors associated with imperfect healing found to be significant at the 1 per cent level, were wound contamination, pain and the presence of a wet or changed dressing at the second examination.


Transabdominal suture of bleeding gastro-oesophageal varices in cryptogenic cirrhosis of the liver. Emergency transabdominal suture of gastro-oesophageal varices was performed when conventional conservative measures including oesophageal tamponade failed to control bleeding in 60 of 167 patients with cryptogenic cirrhosis and bleeding varices. The immediate mortality for the whole series was 29-9 per cent. Surgery performed in this selected manner carried an immediate mortality of 40 per cent. The transabdominal approach detected and treated 19 (31-7 per cent) patients who had concomitant bleeding from extra-oesophageal sources. Ageing and sex (male) affect the immediate prognosis adversely. Using a modification of Child's classification of hepatic dysfunction, a direct relationship between hepatic dysfunction and mortality was found, reaching 100 per cent in those with grade C (severe) dysfunction, irrespective of whether or not surgery had been performed. Bleeding was successfully arrested in 96-7 per cent of cases and recurrence of bleeding was acceptably low in the first 6 months of surgery but not after.


Treatmenf of optic neuritis by retrobulbar injection of triamcinolone. In a single-blind controlled clinical trial patients with optic neuritis caused by demyelination were given a single retrobulbar injection of triamcinolone. Though the treated group showed a trend towards more rapid recovery of vision than the controls, there was no significant difference in visual acuity, colour vision, or visual fields during the first six months after treatment. We conclude that routine use of corticosteroids is not justified in unilateral optic neuritis when vision in the other eye is good. Shortening the period of visual disability in bilateral disease or unilateral disease when vision in the other eye is poor, however, may be justifiable.


"Right" stay in hospital after sugery: randomised controlled trial. A randomised controlled trial was carried out on 100 patients to compare the effects of discharge after certain pre-specified clinical criteria had been fulfilled--"right" stay--with those of discharge at an arbitrary 10 days after surgery--"fixed" stay. The operations concerned (cholecystectomy and vagotomy) were more hazardous than those previously included in studies of early discharge. Patients in the right-stay group were discharged, on average, 7-6 days after operation--that is, two days earlier than those in the fixed-stay group. In terms of clinical progress, social factors such as return to work, and the acceptability to patients and relatives of the implications of right stay, patients in this group fared as well as those in the fixed-stay group, and in some respects slightly better. Right stay entailed the transfer of some work from hospital to community medical and nursing staff, but this also was acceptable. The concept and use of the right-stay principle is of value in planning the postoperative discharge of suitable patients.


Sequential treatment with quinine and mefloquine or quinine and pyrimethamine-sulfadoxine for falciparum malaria. Patients with falciparum malaria were studied in Thailand, an area of known chloroquine resistance. The patients were unselected and some had severe malaria, and they were randomly assigned to one of two sequential regimes. A short course of quinine (average 4 doses, equivalent to 2 g base) followed by a single dose of pyrimethamine-sulfadoxine (Fansidar) cured 92% of patients (36 out of 39), while a short course of quinine followed by a single 1-5-dose of mefloquine cured all of the 35 patients who could be followed up. Gastrointestinal side effects were minimal if at least 12 hours elapsed between the last dose of quinine and the mefloquine. Sequential quinine and mefloquine is the most effective treatment for patients with chloroquine-resistant falciparum malaria, including those with severe or complicated disease. Mefloquine, however, is not commercially available, and the similar regimen using Fansidar is almost as effective.


Peptic ulceration, gastric secretion, and renal transplantation. Fifty-four patients on haemodialysis for chronic renal failure underwent renal transplantation. Basal and maximum acid output and the incidence of peptic ulcer before transplantation were not significantly different from those of controls. But after renal transplantation the incidence of symptoms of peptic ulcer was high (22%) and four out of six patients who developed gastrointestinal bleeding died from this complication. In men peak acid output was significantly increased after renal transplantation and was associated with a 30% incidence of symptoms of peptic ulcer compared with 10% in women, who showed no significant change in mean basal or peak acid output. Peptic ulceration after transplantation was not associated with steroid dosage, hyperparathyroidism, or the height of blood urea concentrations. Given criteria of a history of dyspepsia, abnormal barium meal findings, or gastric hypersecretion, it was not possible to identify patients at risk from peptic ulceration or life-threatening complications after renal transplantation. Thus the routine screening of these patients for peptic ulcer has no practical value, and the incidence of fatal complications is not high enough to justify routine prophylactic anti-ulcer surgery aimed at reducing acid secretion before renal transplantation.


BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. The Medical Research Council's trial of BCG and vole bacillus vaccines in the prevention of tuberculosis in Great Britain has ended after 20 years' follow-up of the 54 239 participants, who were aged 14 to 15 years when the entered the trial in 1950-2. Participants who were tuberculin positive on entry were left unvaccinated; those who were tuberculin negative were allocated at random to an unvaccinated or to a vaccinated group. The protective efficacy of each of the two vaccines, among those initially tuberculin negative, was 84% during the first five years, and gradually decreased, averaging 77% for each vaccine over the whole period. The incidence of tuberculosis decreased substantially in all groups during the trial, however, and of the total of 610 cases of tuberculosis only 27 developed between 15 and 20 years. Thus we cannot make a reliable assessment of efficacy during this final period. The prevalence and incidence of tuberculosis in Great Britain have decreased radically since this trial began. The expected benefit from large-scale BCG-vaccination of children is now far less, and may decrease further if the incidence of tuberculosis continues to decline.


Comparison of growth inhibition and immunofluorescence tests in serotyping clinical isolates of Ureaplasma urealyticum. Typestrains of the eight serotypes of Ureaplasma urealyticum and 39 genital isolates were typed by the growth inhibition (GI) and indirect immunofluorescence (IF) tests. The GI test proved to be very specific and simple, demanding large volumes of serum. It was less sensitive than the IF test, which produced more cross-reactions, was economical in serum, and able to detect mixed infections. Of the 39 isolates, 27 were serotyped by GI and 34 by IF. Mixed cultures occurred in as many as 36% of the isolates.


Comparison of ornidazole and tinidazole in single-dose treatment of trichomoniasis in women. A comparison is made between oral ornidazole in a single 1-5 g dose and tinidazole given in a 2 g dose using a double-blind technique. All the 45 women with Trichomonas vaginalis infection who were treated with ornidazole were cured. In the tinidazole-treated group 41 out of 43 women had negative cultures after treatment. Tolerance was good in both groups.


[Immuno-cytologic study of hypothalamic LH-RH neurons of the human fetus]. The immunocytological study of LH-RH producing neurons was carried out on 3 newborns and 14 fetuses (from 10 to 36 weeks of age). Perikarya and fibers which were immunoreactive to anti-LH-RH IS were revealed by IF or IE in all the hypothalamus beginning with the 13th week. Important variations in neurons staining may translate "physiological" differences in their LH-RH charge but can be also the result of the diverse technical conditions. In three 16-week-old female fetuses, the large number of neurons (more than 150 per hypothalamus) permitted a good topographical and morphological study of them. They are scattered in vast areas of the anterior hypothalamus (lamina terminalis (LT) and septum), mediobasal and premammillary hypothalamus. The fibers which are particularly immunoreactive in semi-thin sections form a large hypothalamo-infundibular contingent in the posterior lip of the ME where they give rise to collaterals that terminate in contact with the capillaries of the mantelplexus, this taking place both before and after the apparition of the intra-eminential loops at the 16th week. Numerous in the LT, they terminate around the deep capillaries of the vascular organ or in contact with the ependymal epithelium. Some extra hypophyseal fibers go towards the epithalamus and the mesencephalon. To conclude, very early, in the human fetus the peptidergic LH-RH system resembles that described in adult primates; its role in the maturation and control of the gonadotropic cells is evoked.


Orientation detectors in the primary somatosensory neocortex of the raccoon. An analysis of response properties of single neurons in the forepaw region of the primary somatosensory neocortex (SI) of the raccoon was undertaken to gain a better understanding of the neural bases of tactile form discrimination. In the course of this investigation a new type of feature detector neuron which responded preferentially to tactile stimulus orientation was discovered. Within a sample of 110 neurons responding to light touch, two categories of cells were noted in terms of the type of stimulation best able to excite them. One category (linear units) was preferentially responsive to indentations of the skin using a narrow elongated stimulus probe applied in a particular orientation. The other category (round field units) gave a maximum response to stimulation with a round stimulus probe applied anywhere within a roughly circular receptive field. The response pattern of some SI neurons to a maintained indentation of the skin consisted of early and late excitatory responses, separated by a depression in responding. The second excitatory response appeared to be more influenced by variations in stimulus parameters than was the first.


Positional hypoxaemia following post-traumatic pulmonary insufficiency. The effect of body position on ventilatory function was evaluated in a patient with unilateral lung disease. The patient's pulmonary dynamics were examined in the supine, right, and left decubitus positions under conditions of positive pressure ventilation with zero end-expiratory pressure (ZEEP) and 5 cm H2O (0.9 KPa) positive end expiratory pressure (PEEP). When the patient was positioned so that the "diseased" lung was dependent, there was a marked decrease in PaO2 and increase in venous admixture when compared to the values in the supine position. These changes were relatively greater in the ZEEP, than the PEEP situation. When the "diseased* lung was not dependent, there was an increase in PaO2 and a decrease in venous admixture. This was most pronounced when PEEP was applied. Changes in body position may result in clinically significant alterations in pulmonary gas exchange, especially in patients with pre-existing pulmonary dysfunction.


Modulation of pituitary responsiveness to LHRH by androgens in ovariectomized female rats. The effect of androgens on pituitary response to luteinizing-hormore-releasing hormone (LHRH) and their ability to modify effects of 17beta-estradiol (E2) on pituitary responsiveness to LHRH were tested in ovariectomized rats maintained on a daily dose of 0.25 microgram estradiol benzoate per rat for 6 d before androgen administration. Testosterone propionate (TP) (4, 40, 400, or 4000 microgram per rat), administered 24 h before LHRH (500 ng per rat), had no significant effect on luteinizing hormone (LH) or follicle-stimulating hormone (FSH) response. Similar doses of dihydrotestosterone (DHT) did not significantly alter the LH response but significantly suppressed the FSH response. Even the lowest dose completely blocked the FSH response to LHRH. TP in combination with 4 or 400 microgram of E2 suppressed the stimulatory effect of E2 on both LH and FSH response to LHRH in a dose-related manner. DHT and E2 in combination affected LH response inconsistently, whereas their ratio determined FSH response; there was pronounced inhibition of FSH response in rats given high doses of DHT combined with low doses of E2; DHT inhibition of FSH response in animals receiving 4 microgram of DHT with 400 microgram E2 was partially overcome by the stimulatory effect of E2. Our results indicate that TP and DHT affect LH and FSH response to LHRH differently. The ratio of androgen to estrogen is important in determining the response to LHRH.


A rapid fluorescent focus-inhibition test for determining the neutralizing-antibody response to lymphocytic choriomeningitis virus. Levels of neutralizing antibody to lymphocytic choriomeningitis (LCM) virus in the sera of 66 infected persons were assayed by a rapid fluorescent focus-inhibition test (RFFIT). The test was more sensitive than the mouse-neutralization (MN) test and could be completed in less than 24 h. The RFFIT titers were compared with titers obtained by the indirect fluorescent-antibody (IFA) and complement-fixation (CF) tests. Neutralizing antibody detected by the RFFIT remained positive after IRA, CF and MN antibodies had disappeared. The RFFIT for detection of LCM antibody is specific and reproducible and seems especially useful for determining the incidence and epidemiology of LCM virus infections.


Improved procedure of selective enrichment of Shigella in the presence of Escherichia coli by use of 4-chloro-2-cyclopentylphenyl beta-D-galactopyranoside. A previously described procedure for the selective enrichmen of Shigella in competition with E. coli has been modified and tested with a total of 48 strains of the four Shigella species. The new enrichment medium consists of 1,5-strength trypticase soy broth, 1 mM 4-chloro-2-cyclopentylphenyl beta-D-galactopyranoside (CPPG), 0.25% lactose, and 0.1 M citrate buffer (pH 6.2). In competition with a 1000-fold higher population of E. coli than Shigella, 42 of 48 strains from the four species of Shigella were selectively enriched by the new method. Different lots of CPPG did not appear to affect the performance of the medium.


The capsular network of Klebsiella pneumoniae. Attempts at improving chemical fixation for electron-microscopic observation of the capsule of Klebsiella pneumoniae were made. The capsule was preserved by using alcian blue - lanthanum and tris-(1-aziridinyl) phosphine oxide (TAPO) - aldehyde - osmium procedures. Despite the different retention of the overall capsular material and minor variations in morphological details, in both cases the interpretation of ultrastructural patterns suggested that the capsule be composed of a meshed network of thin polysaccharide fibrils radiating from the cell wall. This organization is in keeping with all recognized chemical properties of bacterial polysaccharide capsules or, at least, does not contradict them. Moreover, an effective preservation of bacterial structures other than capsule has been obtained, mostly in specimens fixed by the TAPO-aldehyde-osmium method, a fact which gives further reliability to the technical approach used for capsule visualization.


Induction of multispored asci in two-spored strains of Saccharomyces cerevisiae by amitrole. Although growth of two yeast strains characterized by consistent production of two diploid spores per ascus was inhibited in complex presporulation media containing amitrole, a fraction of the cells produced were able to form asci with more than two spores after transfer to acetate sporulation medium. Cells grown in a defined presporulation medium containing amitrole did not acquire this ability. The increase in spore numbers per ascus is attributed either to the induction by amitrole in growth medium of cells with more than one nucleus or to the restoration of normal meioses in the multispored asci.


Eburicol, lichesterol, ergosterol, and obtusifoliol from polyene antibiotic-resistant mutants of Candida albicans. Two classes of polyene-resistant mutants were isolated from survivors of N-methyl-N'-nitro-N-nitrosoguanidine treatment of a wild-type Candida albicans. An analysis of the major sterols of one class revealed an accumulation of lichesterol and fecosterol while the other class accumulated eburicol, obtusifoliol, and lanosterol with minor quantities of C28 sterols.


Preferential inhibition of phosphatidyl ethanolamine synthesis in E. coli by alcohols. Growth of E. coli in the presence of alcohols of chain lengths 1 through 8 results in an increase in the relative abundance of phosphatidyl glycerol. This results primarily from the preferential inhibition of phosphatidyl ethanolamine synthesis. This inhibition appears to be unrelated to membrane fluidity or to changes in fatty acid composition caused by alcohols. Alcohol-induced changes in total fatty acid composition are reflected in all phospholipid classes. Phosphatidyl serine synthetase is proposed as the most likely site for the effects of alcohols on phospholipid synthesis.


Phage types of Mycobacterium bovis, substrains of BCG. Nineteen substrains of Mycobacterium bovis, strain bacille Calmette-Guérin (BCG) used in laboratories throughout the world for the preparation of BCG vaccines were phage-typed with a battery of mycobacteriophages. The results revealed differences in their susceptibility to phage lysis that allow subdivision of these strains of BCG into two or more phage types.


Enumeration of Clostridium botulinum spores in meats by a pour-plate procedure. Colonies of Clostridium botulinum could be easily distinguished from meat particles by supplementing Wynne agar with 0.4% egg yolk. The pour-plate method was suitable for enumeration of C. botulinum, provided the medium was covered with a layer of agar containing 0.01% dithiothreitol. Viable counts of heat-treated spores were consistently higher in Wynne agar supplemented with egg yolk (Wynne-EY agar) than in Wynne agar alone.


Normal processes and restraints in wound healing. Wound healing normally follows an uninterrupted course but, for the purposes of description, it can be considered in four phases -- hemostasis, acute inflammation, repair and consolidation. Arrest of healing may occur at any phase and lead to a number of clinical problems. Repair cannot begin until the phase of acute inflammation has begun to subside; this fact is of special importance in clinical surgery. Wound healing in gastrointestinal tract and abdominal incisions is emphasized because healing problems are common in these areas and failure to heal results in morbidity and a regrettable mortality.


Management of cardiac arrest: seven steps to survival. Cardiac arrest is a common medical emergency. It usually occurs suddenly and results in irreversible brain damage unless prompt, effective treatment is instituted. One plan for dealing effectively with this emergency consists of seven steps of cardiopulmonary resuscitation: (1) establishing the diagnosis and deciding whether to resuscitate; (2) administering a precordial thump, noting the time and summoning aid; (3) establishing a patent airway and performing artificial ventilation and external cardiac compression; (4) instituting general supportive measures; (5) diagnosing the cardiac arrhythmia responsible for the arrest; (6) treating the arrhythmia; and (7) managing the patient after resuscitation.


Prevention of congenital rubella.

Prevention of congenital rubella. The vaccine of choice for rubella vaccination is considered to be RA 27/3, based on frequency of side effects, duration of immunity, antigenic potential and rate of reinfection by wild virus. The most appropriate individuals to be vaccinated are prepubertal schoolgirls and susceptible members of other high-risk groups, and a nationwide immunization program is suggested. Premarital determination of rubella-immune status should be mandatory for all women of childbearing age. A favourable cost/benefit ratio for rubella vaccination seems highly probable. The use of a rubella "fact sheet" to provide education and information for those at risk is strongly recommended.


Fatal histiocytic lymphoma of the brain associated with hyperimmunoglobulinemia-E and recurrent infections. A 10-year-old girl with eczema, asthma, recurrent abscesses, middle ear infections and pneumonias developed a histiocytic lymphoma of the brain. Immunologic evaluation revealed hyperimmunoglobulinemia E, depressed neutrophil chemotaxis, absent delayed hypersensitivity skin test tests, low T-lymphocyte numbers and depressed in vitro lymphocyte responses. The occurrence in this patient of a histiocytic lymphoma, which is commonly associated with more classic immunodeficiency syndromes or immunosuppression for transplantation, suggests that individuals with hyperimmunoglobulinemia E and recurrent infections may also be at increased risk for developing unusual malignancies.


Conservative local treatment of breast cancer. A survey of controlled randomized trials of orthodox therapy directed to the breast and axillary nodes has indicated that 1) if radical mastectomy is performed, postoperative radiotherapy gives no advantage over a watching policy and 2) if postoperative radical radiotherapy is given, there is no need for other than a simple mastectomy. A large multicenter trial is also indicating that simple mastectomy alone with reservation of radiotherapy for treating local recurrent disease is safe initial treatment. These results refer to survival; postoperative radiotherapy does reduce the incidence of local recurrence but this apparently can be equally well treated when it occurs. Local excision of the tumor, followed by radiotherapy, has been reported to give inferior results to a radical approach in Stage II tumors.  Recognition that all these methods of local treatment fail to cure the majority of patients has emphasized the need to define the extent of the disease and to apply treatment according to that extent. We have studied a policy of selective local therapy based on this principal in which total mastectomy is combined with biopsy of the pectoral lymph nodes and further treatment by radiotherapy given only if these nodes are involved by tumor. This policy has been compared with a standard radical approach and is giving similar results. In our current Edinburgh trials, pectoral node biopsy is also used to select patients for inclusion in trials of systemic therapy.


Conservative treatment of breast cancer. A trial in progress at the Cancer Institute of Milan. The report describes a clinical trial on conservative surgery in progress at the National Cancer Institute of Milan, Italy. The randomized clinical trial compares radical mastectomy with a more conservative procedure consisting of mammary resection plus axillary dissection plus radiotherapy. The resection comprises an entire quadrant of the breast together with the overlying skin and the corresponding portion of the fascial sheet of the pectoralis major. The axillary dissection is performed in continuity with the resected breast quadrant except in cases with tumors of lower inner quadrants, who need two separate incisions. After surgery the patients receive 6000 rads to the residual breast tissue over five to six weeks, starting 15 days after operation. The cosmetic results are satisfactory in approximately 70% of cases. The trial is limited to cases with tumors less than 2 cm and no palpable axillary nodes (T1N0M0). Patients with histologically positive lymph nodes (N+) are submitted to adjuvant chemotherapy with CMF for one year. From September 1973, to October 1976, 331 cases entered the trial. One hundred sixty were treated with radical mastectomy and 164 with the conservative procedure. Axillary metastases were found in 23% of the radical and in 29% of the conservative surgery group. Four local-regional recurrences have occurred till now, two in each group. Five cases in the radical mastectomy group and one in the conservative group had distant metastases. The clinical trial will collect some 500 cases by the end of 1977 and significant preliminary results are expected to be available from 1978.


The CMF program for operable breast cancer with positive axillary nodes. Updated analysis on the disease-free interval, site of relapse and drug tolerance. In a prospective randomized study adjuvant combination chemotherapy with CMF was administered for 12 monthly cycles to 207 patients subjected to radical mastectomy (Halsted or extended) and treatment failure was compared to that observed in 179 patients whose primary therapy consisted only of radical surgery (control group). All patients of both groups had histologically positive axillary lymph nodes. At three years from mastectomy the total failure time distribution was 45.7% in control patients compared to 26.3% in women given CMF (P less than 0.0001). New disease manifestations were higher in the subgroup with four or more nodes (64.9% vs 41.5%) compared to that with one to three nodes (37.9% vs 19.1%). Premenopausal controls showed a progressively higher incidence of treatment failure compared to CMF patients (P=0.00001). The decreased recurrence rate in postmenopausal women given CMF was appreciable only during the first 12 months. From this time on, the difference no longer existed. The cumulative percent of recurrence in patients without or with drug-induced amenorrhea (27.2% vs 9.2%) was not statistically significant. At three years 21.4% of control patients have died of progressive cancer compared to 10.4% of CMF patients. The difference in the survival curves was not significant (P=0.08). Toxicity was moderate and reversible. No drug induced neoplasm was observed. Present results confirm the efficacy of 12 CMF cycles in premenopausal patients. Postmenopausal women probably require a more intensive and prolonged adjuvant chemotherapy.


Current status of estrogen and progesterone receptors in breast cancer. Breast cancer is often hormone responsive, since growth or regression of tumors can often be modulated by appropriate endocrine manipulations. Estrogen and progesterone appear to be major hormones involved in regulation of breast tumor growth. It has been recently argued that a more accurate marker of hormonal responsiveness might result if an end product of an intact estrogen response system were measured instead of the initial hormone binding step. Progesterone receptor (PgR) has been investigated in this regard since it can be readily measured in human breast tumors and there is clear evidence in experimental breast tumor model systems that PgR is under acute estrogen control. PgR is rarely found in ER- metastatic breast tumors but is present in approximately 59% of ER+ metastatic tumors, especially in those tumors with high levels of ER. Preliminary clinical correlation of ER, PgR and response to endocrine therapy is encouraging. The response rate is significantly higher if the tumor contains both ER and PgR than if the tumor contains ER alone.


Antiestrogens in treatment of breast cancer. The antiestrogens represent a group of compounds, not necessarily steroidal, which are able to decrease the specific uptake of estrogens in vitro and in vivo by various target tissues in the rat and in man. This action is explained either by competitive binding to estrogen receptor sites or, more probably, by failure of the antiestrogen complex, translocated into the nucleus, to stimulate neoformation of receptors in the cytoplasm. This explains the transient estrogenic effect of antiestrogen. Antiestrogens used in humans are hormone specific and antagonize also non-steroidal estrogens, like stilbestrol. Three compounds have been used in advanced breast cancer with the same indications as the older hormonal treatments. They are clomiphene citrate, nafoxidine and tamoxifen. Nafoxidine and tamoxifen are probably equally active. The response rate is between 28 and 35%, with a median duration of nine months. Nafoxidine is toxic for the skin and tamoxifen is the preferred compound. A randomized trial comparing ethinyl estradiol and an antiestrogen showed similar rates of response with the two compounds in advanced breast cancer. The uniformity of results of treatment of advanced breast cancer by hormonal agents including antiestrogens and their limitations, probably justifies the present-day concept which assigns hormonal treatment a secondary role, either as a supplement to cytotoxic chemotherapy or for old and debilitated patients. However, as a supplemented to chemotherapy, hormonal agents are probably important since recent studies have shown that apparently all breast cancers have positive receptor sites, albeit in variable amounts. Because of their lack of toxicity, antiestrogens are probably the best hormonal agents available at present.


Adaptation of an automatic bacterial colony counter for measuring lung tumor growth in mice. Adaptation of an automatic bacterial colony counter proved to be an efficient procedure for detecting and quantitating tumor growth in mouse lungs prepared by the Wexler method of India ink insufflation. After correlation of the size discriminator settings on the automatic counter with the Wexler visual scale, the amount of tumor growth in the lungs of 52 mice was determined by eye and independently by the automatic counter. There was no statistical difference between the two procedures. When the mouse lungs were grouped according to the number of tumors computed by eye, there was no statistical difference between the two counting procedures in any of the groups. The standard deviation was independent of the number of tumors in the lungs. This caused the precision of the automatic counter to be poor in lungs with few tumors because the error was a greater percentage of the total. In lungs with a large number of tumors, which were difficult to count by eye, close agreement between the two methods of counting was demonstrated.


The chemotherapy of advanced bladder carcinoma. This paper is a summary of the clinical chemotherapy of metastatic or recurrent bladder carcinoma. Mitomycin C, doxorubicin, methotrexate, and 5-fluorouracil appear to have cytotoxic activity against bladder carcinoma when used as single agents, although the reported objective responses to each agent vary greatly. Cyclophosphamide in intermittent high i.v. doses produced an objective response in 4 of 10 patients treated by the author, and other reports suggest that this drug also may have activity against bladder cancer. cis-Dichlorodiammineplatinum is a new drug that also deserves further study.


The pathogenesis of experimental bladder cancer. The pathogenesis of signal morphological lesions of the urinary bladder induced in several species following administration of N-butyl-N-(4-hydroxybutyl)nitrosamine, bracken fern, or N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide is presented. Incidences of bladder neoplasia exceeding 80% were generated in the rat by each compound. Bladder neoplasia was induced in the following species by each substance: by N-butyl-N-(4-hydroxybutyl)nitrosamine in the mouse, hamster, guinea pig, and dog; by bracken fern in the guinea pig, mouse, and cow; and by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in mouse, hamster, and dog. The guinea pig appeared resistant to the bladder oncogenicity of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. Different species displayed a gradient of bladder neoplastic responsiveness. Hyperplasia was a consistent early lesion and was usually focal. Early hyperplastic lesions regressed following removal of the carcinogenic stimulus, but later lesions appeared to be irreversible. These animal systems appear useful in providing opportunities for investigations relevant to human bladder cancer.


Some immunological considerations relevant to the study of human bladder cancer. The likelihood that immunosurveillance, concomitant immunity, and immunodepression play a role in the development and spread of neoplasms of the urinary bladder is discussed. The circumstantial evidence for the existence of concomitant immunity to bladder cancer-associated antigens is briefly reviewed, and the implications of the hypothesis of Zinkernagel and Dougherty of a genetic restriction to the cytotoxicity of T-cells for virally determined target cell antigens and of the concept of immunoregulatory cells for our understanding of the immunology of bladder carcinoma are discussed.


Classification of the bladder cancer patient based on in vitro measurements of the immune response. In vitro measurements of the immune response in patients with cancer can be divided into those that estimate nonspecific and those that estimate tumor-specific immune responses. Contained herein is a review of these measurements, especially as they relate to studies that have been reported in patients with transitional cell carcinoma (TCC). In vitro tumor-specific immunity has been extensively examined in TCC using the lymphocyte-mediated microcytotoxicity assay, but subsequent observations on this assay have seriously jeopardized the validity of those early findings. Recent modifications of this assay have permitted longitudinal studies of lymphocyte cytotoxicity in TCC patients, and clinical correlations suggest that this modified assay may detect important immunological events. To date, however, a clinically useful classification of the TCC patient based on in vitro measurement of immune responses has not been achieved, although many promising areas still require investigation.


Development and application of basic research techniques in bladder cancer research. The growth of transitional epithelial cells with different growth media and growth supports was examined. Sephadex G-10, Bio-Gel P-20, Bio-Glas-1000, DEAE-Sephadex A-50, DEAE-cellulose, CM-Sephadex C-50, acid-soluble collagen, and immobilized collagen fibers were used to enhance plating efficiency. Acid-soluble collagen layers optimally increased the plating efficiency of primary cultures of bladder carcinoma. Media alterations with serial combinations of fetal calf, newborn calf, calf, bovine, and bull serum with minimum essential medium, Roswell Park Memorial Institute Tissue Culture Medium 1640, Connaught Medical Research Laboratories Medium 1066, Medium 199, Grand Island Biological, National Cancer Tissue Culture 135, 1415, McCoy's 5A, and National Cancer Institute medium were established. No promotion of cell division was noted with any one of these basic medium formulations.


Studies on the prostate and testis as immunologically privileged sites. The immunology of the prostate and testis was studied by observing allograft survival in rats and by measuring humoral antibody and delayed hypersensitivity responses to tissue antigens in the rabbit. The delayed hypersensitivity response to tissue antigen(s) was definitely diminished in those organs without demonstrable afferent lymphatics (ie, prostate, anterior eye chamber) while the humoral response was unaffected. Allograft survival in the rat showed prolonged survival in the testis and anterior eye chamber with intermediate survival in the prostate and muscle and abbreviated survival of orthotopic grafts. The extraordinary incidence of prostatic carcinoma with increasing age is discussed in light of these data. The apparent paradox of the testis as an immunologically privileged site remains unexplained.


Calibration of densitometers for indicator dye dilution. A systematic investigation was undertaken to determine which factors affect the calibration of a Gilford monochromatic densitometer used for recording indicator-dilution curves with indocyanine green. Calibration was not influenced by variation of withdrawal speeds from 6.4 to 20.6 cm3/min but varied with differing sampling systems. Variation in haemoglobin from 10 to 17.5 g-dl-1 or in haematocrit from 30 to 60% did not affect calibration. Calibration lines showed both curvature and hysteresis. The opitcal properties of indocyanine green were not affected by storage of diluted dye in the dark for 24 hours but were altered by the presence of contrast media used in angiography. No systematic error resulted from the substitution of stored ACD blood for patient's blood in calibration although random error was increased. Recommendations based on these findings are made for a simple calibration technique which avoids systematic error.


Androgen receptors in human prostatic tissues: a review. Methods for the measurements of androgen receptors in the human prostate have been reviewed. The differentiation of binding to receptor from binding to a contaminating serum protein, testosterone-estradiol binding globulin (TeBG), has been the major problem in the establishment of a reliable assay in man. Charcoal adsorption and Sephadex gel filtration (G-25) have been the simplest methods utilized, but unfortunately they do not eliminate binding to TeBG. Although other methods such as sucrose density gradient centrifugation, ion-exchange chromatography, and protamine precipitation are more specific for the measurement of the androgen receptor, they have not been uniformly reproducible and are too elaborate for easy clinical applicability. For clinical purposes, assays using potent synthetic androgens that do not bind to TeBG or anti-steroid antibodies may prove to be the methods utilized in the future to measure the androgen receptor content of human prostatic tissue.


Phase I trial of ftorafur combined with mitomycin C or methyl-CCNU in gastrointestinal cancers. Twenty-five patients with disseminated gastrointestinal malignancies were treated in a phase I study with a combination of ftorafur and mitomycin C or florafur and methyl-CCNU. Most patients had been heavily treated previously. Gastrointestinal, central nervous system, and marrow toxicity were manageable. Tumor regression was noted in five of 25 patients. A large-scale phase II study in untreated patients with gastrointestinal malignancies appears indicated with a combination of these agents.


Methods for determining the proliferation kinetics of cells by means of 5-bromodeoxyuridine. After treatment of cells with 5-bromodeoxyuridine (BUdR), the percentage of completely BUdR-labelled interphase nuclei is greater the longer the BUdR treatment. The labelling effect is visible after staining with the fluorochrome 33258 Hoechst and with Giemsa. Various formulae and a nomogram are presented by means of which the percentage of cells in S period, duration of the S period and the whole cell cycle can be determined by examination of a single preparation or by comparison of several preparations. The methods are tested using cell cultures of Microtus agrestis and compared with autoradiographic methods after labeling with 3H-thymidine.


Studies on the population kinetics of the Walker carcinoma by autoradiography and pulse cytophotometry. The proliferation parameters of the Walker carcinoma were estimated from both in vivo and in vitro measurements. tthe transplantable Walker carcinoma 256 was grown in male inbred BD1 rats. During exponential growth, 5--6 days after transplantation, a PLM curve was performed, yielding estimates of TC approximately equal to 18-0 hr, TS approximately equal to 6-4 hr, TG2+M approximately equal to 4-1 hr. With the double labelling technique in vitro under 2-2 atm oxygen we obtained: TC approximately equal to 18-2 hr, TS approximately equal to 8-2 hr, TG2+M approximately equal to 2-0 hr. From pulse cytophotometry DNA content histograms the fractions of cells in the cell cycle phases were calculated using a computer program: fG1 approximately equal to (47-6 +/- 1-1)%, fS approximately equal to (34-1 +/- 1-0)%, fG2+M approximately equal to (18-3 +/- 1-5)%. These fractions remained constant between the fifth and the twelfth day after transplantation. At that time the tumour growth had already slowed down appreciably. The growth fraction determined by repetitive labelling was 0.96 on the fifth and 0-93 on the seventh and eleventh day. The cell loss factor was phi approximately equal to 17% during exponential tumor growth and increased to about 100% between the tenth and twelfth day. The agreement of the cell kinetic data determined by autoradiography from solid tumours in vivo (PLM, continuous labelling) and autoradiography as well as pulse cytophotometry from in vitro experiments (excised material) was satisfactory.


A historical review of the concept of the left ventricle as a pump. Although the concept of the left ventricle as pump has gradually evolved over the past 2000 years, the "modern era" of our understanding began in the 1880's. Studies by Howell and Donaldson, using an isolated heart-lung preparation, provided insight into the inter-relationship between preload, afterload and contractility. These concepts were further advanced by Frank, Henderson and Starling, all using isolated heart preparations. The development of new techniques by Wiggers and Hill in the 1920's and 1930's opened up entirely new areas of investigation using intact animal preparations (Wggers) and isolated muscle segments (Hill). Our debt to these investigators is enormous, and its is perhaps appropriate to reflect on their creative energies as we attempt to define more clearly the mechanical and biochemical functions of heart muscle.


Restoration of normal morphology, adhesion and cytoskeleton in transformed cells by addition of a transformation-sensitive surface protein. Transformed cells lack a large, external, transformation-sensitive (LETS) glycoprotein which is a major surface component of their normal counterparts. Addition of LETS glycoprotein isolated from normal cells to transfomed cells restores certain morphological features and adhesive properties characteristic of normal cells. LETS protein is detected on the cell surface both by iodination using lactoperoxidase and by immunofluorescent staining. The surface distribution pattern detected by immunofluorescence is strikingly similar to that of normal cells. After addition of LETS protein, transformed cells also exhibit well defined actin cables which are not seen in untreated, transformed cells. All these alterations can be blocked by treating LETS protein with specific antisera or by subjecting it to mild trypsinization prior to addition to transformed cells. The effects are rapidly reversible by mild trypsinization, which removes the added LETS protein. The high rate of uptake of 2-deoxyglucose, characteristic of transformed cells, is not affected by LETS protein. These results suggest that LETS protein may have a role in cell attachment and spreading, and affect the organization of cytoskeleton.


Anomalous synthesis of ppGpp in growing cells. In E. coli cells, accumulation of ppGpp is normally triggered by conditions that restrict the aminoacylation of tRNA or interfere with carbon/energy source metabolism; in both cases, the nucleotide's accumulation is associated with control of stable RNA synthesis and is generally believed to bring it about. We have found an anomalous situation wherein vigorously growing cells accumulate a high level of ppGpp and there is no restriction of stable RNA synthesis. This occurs when wild-type cells are shifted up from an abnormally low growth temperature to one in the optimal range (35 degrees C-40 degrees C). The effect is partly, but not entirely, dependent upon the presence of a functional relA gene product. These results appear to call into question the simpler interpretations of the role of ppGpp in the control of stable RNA synthesis.


Intranasal allergen challenge during corticosteroid treatment. The effect of a corticosteroid drug on type I reactions in the nose was studied in eighteen hay fever patients. They were treated with a daily dosage of 800 microng beclomethasone dipropionate intranasally for I week, in a double-blind, placebo-controlled cross-over trial. Allergen challenge on the last day of each treatment period showed that steroid treatment diminished sneezing and rhinorrhoea, but the effect was not statistically significant (P = 0-10). Immediate nasal blockage was unaffected. There is a marked discrepancy between the minor protection offered by beclomethasone dipropionate in type I allergy, as suggested in this study and the marked efficacy of the drug in the treatment of hay fever. It is suggested that two factors may account for this discrepancy. First, the significance of "delayed" reactions for hay fever symptoms. Second, the difference between a single allergen provocation and continuous exposure. It is suggested that a slight steroid inhibition of immediate reactions following allergen provocation is potentiated during natural exposure due to inhibition of the priming of the end-organ.


The uptake of Aspergillus fumigatus protein by serum IgG antibody from patients with pulmonary aspergillosis. A method is presented for measuring the uptake of Aspergillus fumigatus protein by IgG antibodies from human serum. The human IgG is first isolated with an anti-IgG conjugated immunosorbent and then incubated with radio-iodinated A. fumigatus protein. A group of twenty-three control sera gave the same background levels as tests without sera. The highest uptake of A. fumigatus protein was given by the sera of patients with aspergilloma, and lower values were obtained with six out of thirteen sera from patient's with asthma and twenty-five out of twenty-eight sera from patients with asthma and pulmonary eosinophilia, i.e. allergic bronchopulmonary aspergillosis. These results were in agreement with precipitin tests, Inhibition studies with unrelated antigens showed that the reactions were specific for the A. fumigatus protein, of which more was bound by test sera than with a crude extract.


Homogeneous reactant-labeled fluorescent immunoassay for therapeutic drugs exemplified by gentamicin determination in human serum. We applied a homogeneous reactant-labeled fluorescent immunoassay to the measurement of therapeutic drug concentrations in human serum, exemplified here by gentamicin. A derivative of umbelliferyl-beta-galactoside was coupled covalently to the drug and this conjugate was found to be nonfluorescent under assay conditions. The drug/dye conjugate was a substrate for bacterial beta-galactosidase and yielded a fluorescent product. When the drug/dye conjugate was bound to anti-gentamicin antibody it was inactive as an enzymatic substrate. This inactivation was relieved by the presence of gentamicin in competitive binding reactions. Hence, the rate of production of fluorescence was proportional to the gentamicin concentration. The fluorescent assay yielded values which compared favorably to a radioimmunoassay for gentamicin in clinical serum samples (r=0.94, standard error of estimate=0.66 mg/liter). The fluorescent assay requires only 1 microliter of serum and offers several advantages over existing techniques: sensitivity, specificity, simplicity, and the obviation of radioisotopes.


Enzyme immunoassays with the miniature centrifugal fast analyzer. We studied the EMIT (Enzyme Multiplied Immunoassay Technique, Syva) procedures for the assay of phenytoin and phenobarbital in serum, adapting them to the miniature Centrifugal Fast Analyzer. For different concentrations of drug, each rate of reaction decreased continuously with time, tending to converge on a single common value. The rate was most affected by the concentration of drug almost immediately after the reagents were mixed, less so thereafter. The antibody evidently is present in sufficient excess to bind all the enzyme-labeled drug ordinarily present, but the antibody-bound enzyme was only 75% inhibited; this helps explain the appreciable residual activity when no drug is present. The reaction course was the same whether the serum and enzyme-labeled drug were added to the antibody sequentially or simultaneously, which suggests that antibody is bound to drug appreciably faster than to enzyme-labeled drug. The reaction rates 15 to 30 s after mixing were used as the measure of the drug concentrations. These results were confirmed by noting the rates at successive 15-s intervals. The analyzer yielded a run-to-run CV of 10% for phenobarbital at 30 mg/liter, and 9% for phenytoin at 15 mg/liter, as compared to the 15% quoted by Syva.


The estimation of plasma valproate by gas-liquid chromatography. A gas chromatographic method for the plasma assay of the anticonvulsant, sodium valproate, is described. Derivatization is not necessary. 200 microliter plasma are required for a single estimation. The method involves a chloroform extraction of valproate and the internal standard, cyclopentane carboxylic acid, from acidified plasma. Gas-liquid chromatography using the stationary phase 10% SP-216-PS gives complete separation of valproate and the internal standard in eight minutes. The limit of detection is 20 mumol valproate/1 plasma (equivalent to 40 pmol on column). This is well below the lower therapeutic plasma level. The between-run precision of the method indicates a variation for each sample within+/-3% of its mean value.


An investigation into gonadal dysfunction in patients with idiopathic haemochromatosis. Endocrine studies were performed on twelve patients with proven idiopathic haemochromatosis. Basal gonadotrophin levels and/or their responses to LH releasing hormone (LHRH) were low in nine patients, all of whom showed low plasma testosterone levels and clinical evidence of hypogonadism. Those patients with normal gonadotrophin responses had higher testosterone values, suggesting that the poor testosterone secretion was primarily due to inadequate trophic stimulation. No patient showed hypothyroidism of hypothalamic-pituitary origin, while the cortisol response to hypoglycaemia was normal in all six patients studied. GH responses were more variable and difficult to interpret, since the number of the patients studied was small and the degree of hypoglycaemia after insulin was unpredictable.


Rheumatoid factor plaque-forming cells in rheumatoid synovial tissue. Cells producing rheumatoid factor (RF) were readily detected in vitro by means of a haemolytic plaque assay system employing sheep erythrocytes (SRBC) sensitized with reduced and alkylated rabbit IgG anti-SRBC antibody as target cells. Rheumatoid factor-producing, plaque-forming cells (RF-PFC) were observed in all of the synovial tissue cell preparations from seropositive rheumatoid arthritis patients studied. The numbers of RF-PFC varied considerably without any direct correlation with serum titres of RF antibody activity. However, high numbers of RF-PFC were never found in patients with low rheumatoid factor titres whereas, high and low numbers of RF-PFC were found among the patients with high RF titres. Synovial tissue cell preparations from a group of seronegative patients, with only one exception, failed to exhibit RF-PFC.


Reproducibility of the indirect immunofluorescence test on swollen human spermheads. Sera of 111 vasectomized men and infertile men and women were tested in each of two laboratories with the indirect immunofluorescence test on swollen human spermatozoa to detect antibodies against nuclear antigens specific to sperm. Comparison of the results revealed complete agreement in 110 of the sera. There were seventeen concordant positive sera (eight out of eighteen sera from vasectomized men, eight out of seventeen sera from infertile men, and one out of seventy-six infertile women). Most of the antibodies were of the IgG class.


Schistosoma mansoni: impairment of the cell-mediated immune response in mice. Skin-graft rejection in mice experimentally infected with Schistosoma mansoni is delayed when grafting is performed 60 days after the infection. In mice infected 30 days prior to the grafting, the grafts were rejected at the same time both in infected and in control animals. This observation indicates that impairment of cell-mediated immune response occurs in mice with mature S. mansoni infections.


The effects of prednisolone in leucocyte function in man. A double blind controlled study. The effect of prednisolone on various immunological parameters was studied in patients with ulcerative colitis in complete remission. The study was designed as a double blind trial in which patients received either prednisolone or a dummy preparation and the following observations were made:(1) The mean lymphocyte count fell from 1738 cells per mm3 to 501 cells/mm3 4 hr after prednisolone was given but by 24 hr was significantly elevated to 2399 cells/mm3; thereafter it returned to normal levels. (2) Surface marker assays of lymphocytes forming spontaneous sheep cell (E), Fc (EA), and C3 (EAC) rosettes; and cells bearing surface immunoglobulin fluctuated in approximately the same pattern as the total lymphocyte count. (3) The mitotic response to a sub-maximal stimulating dose of phytohaemagglutinin (PHA) was significantly depressed 4 hr after steroid administration but returned to normal by 24 hr. (4) Spontaneous and PHA-induced lymphocyte mediated cytotoxicity fell significantly by four hours and remained depressed to the end of steroid administration. The PHA-induced cytotoxicity was still significantly depressed 7 days after steroid administration was stopped. (5) K-cell cytotoxicity did not follow the general pattern and was only slightly reduced at four hours being lowest after 24 hr and still depressed 7 days after cessation of steroid administration. (6) The number of plasma cells in the rectal lamina propria showed no significant change after one week of steroid administration. (7) No significant changes occurred in any of the above assays, in the control group. (8) Polymorphonuclear leucocyte counts rose sharply by 4 hr in the patients receiving prednisolone. There was also a smaller but significant rise in the control group. They remained elevated for 7 days in the group receiving prednisolone, and subsequently fell to normal levels. The control group had returned to initial levels by 24 hr.


Rosette formation with mouse erythrocytes. IV. T, B and third population cells in human tonsils. Mononuclear cells from twenty human tonsils and peripheral blood lymphocytes were examined for T, B and 'third population cells'. Compared with peripheral blood lymphocytes, tonsils were found to have a higher proportion of B lymphocytes with surface IgM, IgD and IgA. Mouse erythrocyte rosette-forming cells were also present in increased proportions. However, 'third population cells' were found in very low proportions. Phagocytic cells as determined by latex ingestion and peroxidase staining were also present in low proportions. The lack of 'third population cells' in human tonsils may establish this organ as one of particular interest in the study of lymphocyte subpopulations because T and B lymphocytes can be purified without contaminating 'third population cells'. The role of the third population of lymphocytes in antibody-dependent cytotoxicity and spontaneous cytotoxicity may be supported by the absence of these functions along with absence of the 'third population' cells from tonsilar lymphoid cells.


Urine fibrin degradation products in detection and management of acute and chronic renal transplant rejection. Detection of rejection by serial determinations of urine FDP using the latex agglutination slide test proved to be a reliable, simple and inexpensive method. In the absence of infection, clinical and biochemical acute rejection was preceded by a two-titer rise in excretion of urine FDP in 80% of 26 patients studied. It was not useful in predicting rejection in 44 stable long-term allograft recipients, although persistent elevation of urine FDP after anti-rejection therapy in these patients or those in the immediate post-transplant period implies ongoing rejection. Maintenance immunosuppression should be continued in these patients, but repeated high-dose steroid therapy should be limited because of their poor-term prognosis. Persistent increase in urine FDP may allow selection of those patients who would benefit from a trial of anticoagulant or antiplatelet therapy.


Failure of successful renal transplantation to reverse the dialysis-associated encephalopathy syndrome. A patient is described who had been on home dialysis for two years before receiving a cadaver kidney transplant. In retrospect, minor speech difficulties were noted two weeks before the transplant. A week after the transplant the characteristic speech, movement and electroencephalographic (EEG) abnormalities of the dialysis encephalopathy syndrome abruptly presented. Relentless neurological deterioration ensued ending in death three months later despite excellent function in the transplant. The significance of this observation is related to current theories of pathogenesis.


Diagnosis of urinary tract infection. The interpretation of colony counts. The results of 787 consecutive suprapubic specimens in children were studied. Ninety-two patients with 128 positive cultures were reviewed. Sixty-five children had documented urinary tract infection (UTI) proven by other cultures. Of these, 55 per cent had colony counts less than the traditional 100,000 colony forming units/ml., and 9 per cent had colony counts less than 10,000. Organisms usually regarded as "contaminants" (Staphylococcus epidermidis, mixed organisms) were occasionally proven to cause UTI.


Diuretic therapies in low renin and normal renin essential hypertension. This study was designed to compare the effectiveness of spironolactone, hydrochlorothiazide, and combined spironolactone-hydrochlorothiazide therapy in patients with low renin and those with normal renin essential hypertension. Patients with low renin hypertension had a greater hypotensive response to each regimen (p less than 0.001). Low renin patients responded equally to both spironolactone and to hydrochlorothiazide, and in low renin but not in normal renin patients reduction of blood pressure correlated with weight loss. These results suggest that a volume factor, not specifically related to increased mineralocorticoid production, contributes to the pathogenesis of low renin essential hypertension.


Amelioration of bendrofluazide-induced hypokalemia by timolol. The beta adrenergic blocking drug, timolol, tended to correct the hypokalemia of short-term bendrofluazide treatment in 6 healthy male subjects and although the effect was small it was significant. Timolol also reduced the rise in plasma aldosterone and urine potassium excretion following bendrofluazide and increased the urine sodium/potassium ratio. There was no evidence of a shift of potassium from the intracellular to the extracellular space.


The response to stress.

The response to stress. The normal response to stress can be understood in terms of periods of outcry, denial, and intrusive thoughts leading to working-through to completion. The general physician who understands this pattern can assist the patient through the denial phase by encouraging ventilation and through the intrusive phase by providing structure, advice, and medication to temper the painful feelings. With such assistance, most patients can integrate the stress event into their lives, with the duration of response related to the severity of the stress. A year of stress response after the death of a loved one is common. Psychiatric referral is indicated if the stress response seems unduly prolonged, has lead to maladjustive reactions, is disproportionate to the actual loss, or threatens to overwhelm the person.


Characterization studies on mycoplasmas isolated from bovine mastitis and the bovine respiratory tract. Mycoplasmas isolated from bovine mastitis in California were classified into five distinct species. These included Mycoplasma bovis, M. bovigenitalium, M. alkalescens, M. canadenfe, and an unidentified strain, ST-6. Strains frequently recovered from the nose of young calves proved to be M. arginini, M. bovirhinis was recovered from the respiratory tract but was not a common finding.


Clinical investigations into the effects of practolol in angina pectoris. The value of practolol in the treatment of angina pectoris was studied in three groups of patients by means of different methods. In 23 patients the effect of the drug was evaluated during long-term treatment and in 10 patients in a controlled double-blind trial; in 20 patients, the working capacity was determined by an ECG exercise test on a bicycle ergometer. Long-term treatment revealed advantageous effects of practolol on the incidence of anginal attacks and the number of nitroglycerin tablets consumed in daily life. There was also a noticeable improvement in the ECG. The results obtained in a double-blind trial, with placebo, proved the effectiveness of the drug. The treatment enabled the patients to lead appreciably more active lives. A marked increase in work performance, depending on the dose applied, was confirmed in exercise tolerance tests. No side-effects which would call for discontinuance of the treatment were seen during long-term administration with doses up to 800 mg daily.


An IMV setup without a compressed air source. Intermittent mandatory ventilation (IMV), as described in the literature, utilizes an air-oxygen blender and a compressed air source. When older ventilators are used and in locations in which compressed air sources are unavailable, other arrangements must be made if IMV is to be used. An arrangement is described in which a bird Mark 7 respirator, after the removal of its pneumatic clutch, is inserted into the IMV assembly. Such an arrangement produces wide FIO2 ranges and high flows and obviates the need for an oxygen blender and compressed air source. If a compressed air source is available or if a bird Mark 7 respirator is not available for use, othe arrangements may be more satisfactory.


Differential lung ventilation with PEEP in the treatment of unilateral pneumonia. A technique for differential lung ventilation via a Carlens tube with inspiratory retardation and the application of separate levels of PEEP to each lung are described in the treatment of a patient with severe unilateral pneumonia. In addition to isolating the diseased lung, this technique permits modification of the distribution of ventilation between the two lungs to improve the ventilation-perfusion ratio and enhance arterial oxygenation. Its clinical application is influenced by the flow characteristics of available mechanical ventilators and by the limitations of the currently available double-lumen endobronchial tubes.


EPAP without intubation.

EPAP without intubation. The early institution of end expiratory pressure has been demonstrated frequently to be beneficial in acute respiratory failure. EPAP without intubation allows early therapy while avoiding the complications associated with the high flow rates utilized with CPAP. Three patients are described, illustrating the administration of EPAP for mild ARDS, aspiration penumonia, and postoperative atelectasis.


Mefenamic acid: an under-rated antirheumatic? A double-blind crossover study was carried out in 18 patients with classical rheumatoid arthritis to assess the effectiveness of mefenamic acid (500 mg t.d.s.) compared with placebo or indomethacin (25 mg q.d.s.). Each treatment was given for 1 week and subjective and objective assessments were carried out at the end of each period. Results showed that both mefenamic acid and indomethacin were significantly better than placebo in most parameters. Although duration of morning stiffness and patient preference favoured indomethacin it was considered that there was no demonstrable difference of any clinical significance between the two active medications.


Treatment of acute bacterial infections of the upper respiratory tract. An open comparative study was carried out to assess the effectiveness of 4 antibiotic regimens in eradicating acute bacterial infections of the upper respiratory tract. Patients in each treatment group had similar physical parameters, severity of disease and bacterial pathogens, and were treated for 10 days with either erythromycin estolate, erythromycin stearate, ampicillin or oxytetracycline in the recommended dosage. Each patient was reviewed daily by physical examination and the bacteriological findings from throat swab and salivary washings. The results showed that erythromycin stearate produced more rapid bacterial eradication and clinical resolution of symptoms and fever than with the other antibiotic preparations, and was well tolerated by most patients.


Comparison of sodium meclofenamate and indomethacin in rheumatoid arthritis. A double-blind crossover study was conducted in 15 patients with classical definite rheumatoid arthritis to compare the effect of sodium meclofenamate (300 mg daily) with placebo and indomethacin (100 mg daily). Each treatment was administered for 1 week to patients assigned at random to treatment sequences. The active drugs were shown to be significantly superior to placebo. Sodium meclofenamate alone reduced the articular index. Patient preference, however, was in favour of indomethacin.


A comparison of nystatin cream with nystatin/triamcinolone acetonide combination cream in the treatment of candidal inflammation of the flexures. In a multi-centre double-blind trial, 31 patients with proven bilateral candidal lesions of the flexures were treated for 14 days with nystatin cream on one side and with a combination of nystatin and triamcinolone acetonide cream on the other. Both treatments proved equally effective in terms of mycological cure and clinical improvement. There was a trend in favour of the combination preparation being preferred by both patients and physicians because of more rapid relief of symptoms.