Closed circuit anaesthesia. A new approach.

A logical development of the closed circuit is described, from a basic resuscitation device, through various modifications, to a circle system incorporating an oxygen demand valve, adsorbers for both carbon dioxide and halothane, and some specific safety features. The behaviour of the circuits has been investigated in relation to elimination of nitrogen, concentrations of halothane and circuit leaks.


A passive method of disposal of expired anaesthetic gases.

A passive method for the disposal of waste anaesthetic gases is described. The resistance characteristics of the collector valve, the balancing device and the disposal system were studied. It was found that the resistances offered by the conduction channels and the terminal exhaust valve were extremely low. The collector valves were found to be responsible for most of the expiratory resistance. Swabs taken from various components of the system showed that these were contaminated mainly with commensals and non-pathogenic organisms.


The measurement of anxiety in the pre-surgical patient.

Sixty-nine female patients were assessed for anxiety before receiving premedication. Thirty-three were given lorazepam and 36 were given papaveretum. Re-evaluation 90 min after premedication indicated that lorazepam reduced significantly the level of anxiety, but that papaveretum did not. Anxiety was assessed by means of a five-point nurse-rating scale and the Multiple-Affect Adjective Check List self-rating form. This self-rating anxiety scale was sensitive and proved suitable for recumbent patients in hospital. The test scores compared favourably with previously published values.


Metabolism of 14C-labelled alphaxalone in man.

The metabolism of 14C-labelled alphaxalone, dispensed as Althesin, was studied in normal patients, patients with obstructive jaundice and patients with chronic renal disease and anuria. The radioactive label was removed rapidly from the plasma following i.v. administration. The major portion of the label was excreted in the urine. In patients with normal renal function 14C-labelled alphaxalone is probably taken up by the liver, metabolized to a more polar compound and excreted in the urine; a small amount is excreted in the bile. In the patient with anuria, hepatic uptake appears to be relatively normal and the length of action of Althesin is not prolonged. It is assumed that in such patients the eventual route of excretion is via the bile and faeces.


Intubation of the trachea in the conscious patient.

Intubation of the trachea with the patient awake is sound practice, affording protection against inhalation of gastric contents and against cardiovascular collapse. The writer reviews various methods of awake intubation and describes his own, illustrating it with a discussion of 12 seriously ill patients.


Infantile lobar emphysema. A case report.

A case of infantile lobar emphysema is presented. The period of weaning the infant from the ventilator is discussed, together with some suggestions for the future management of similar cases. Respiratory therapists were used to keep constant surveillance on ventilator function and inspired oxygen concentration. The use of dummies or pacifiers by infants may be detrimental in some instances. Excess humidification may increase airway resistance.


Fractionation of mouse skin carcinogens in cagarette smoke condensate.

The results of a series of mouse-skin paintings are given for fractions prepared by two schemes designed to concentrate the polycyclic aromatic hydrocarbons (PAH) and their heterocyclic analogues (HETC) present in cigarette smoke condensate into single fractions. It is demonstrated that, for each group, a single index of tumour response, the "Weibull risk parameter" (WRP), can be calculated which, considered in conjunction with two other parameters common to all the groups, adequately describes the pattern of tumour incidence in that group. These indices can be used to calculate for each fraction a further statistic, the "tumorigenic ratio" (TR), which conveniently measures the activity of the fraction relative to whole-smoke condensate on a weight-for-weight basis. From the analyses it is shown that the separation processes can successfully concentrate all types of mouse-skin carcinogenic material, irrespective of the type of condensate used, and that a combination of processes prepares an active concentrate representing 2% by weight of the original condensate.


Increased resistance in splenectomized mice to a methylcholanthrene-induced tumour.

Prior splenectomy increased the resistance of BALB/c mice to a syngeneic methylcholanthrene-induced ascitic tumour inoculated i.p. The survival rate of splenectomized mice was 81-6% while those of normal and sham-operated controls were 11-5% and 20% respectively. The effect of splenectomy, however, was seen only within the dose range of 10(3) to 10(4) tumour cells. This effect of splenectomy was abolished by the transfer to mice of serum from tumour-bearing mice, and of spleen cells from normal donors, immediately after the inoculation of tumour cells. Cell-free ascitis fluid did not abolish the effect of splenectomy. The findings suggest that there is a subpopulation of spleen cells which produces a tumour growth enhancing factor which is found in the serum of tumour-bearing mice.


Hypoxic cell radiosensitizers and local control by X-ray of a transplanted tumour in mice.

Tumour experiments including local control after X-irradiation have been performed, using a new technique that eliminates the need for anaesthetics in restraining the animals. This system has been used to investigate the degree of sensitization that can be achieved with ICRF 159 and 4 strongly electron-affinic radiosensitizers, nifurpipone dihydrochloride, metronidazole, Ro-11-3696 and Ro-07-0582. No significant enhancement of the radiation effect was observed with ICRF 159. Significant sensitization was achieved by all 4 nitro-heterocyclic compoinds, Ro-07-0582 being the most effective, metronidazole and Ro-11-3696 the next, and nifurpipone dihydrochloride the least effective. For Ro-07-0582 and metronidazole, several concentrations were investigated, and the interval between injection with Ro-07-0582 and irradiation was varied: an interval of 30 min gave more sensitization than an interval of 90 min. The results from the local control experiments using Ro-07-0582 have been compared with those obtained from regrowth delay experiments. The radiosensitization obtained by the Ro-07-0582 increased with the X-ray dose above 25 gray. Both metronidazole and Ro-07-0582 gave significant enhancement effect at serum concentrations which can be achieved in man.


Cytotoxicity of Ro-07-0582; enhancement by hyperthermia and protection by cysteamine.

The selective cytotoxicity which Ro-07-0582 exhibits towards hypoxic cells is strongly temperature-dependent. This cytotoxicity is reduced by the radical scavenger cysteamine, suggesting that nitro radicals or nitroso intermediates are involved in cell killing by the drug. Chromosome aberrations are not induced by Ro-07-0582 even when the surviving fraction is reduced to 0-01.


Evidence for a common tumour-associated antigen in extracts of human bronchogenic carcinoma.

Xeno-antiserum specific for antigenic components of bronchogenic carcinoma was raised in rabbits, by passively immunizing them to normal human lung antigens at the same time as immunization with a tumour extract from a squamous-cell carcinoma. Antiserum so raised contained minimal quantities of anti-normal antibody which could be removed by a single absorption with glutaral-dehyde-insolubilized normal lung extract. When tested by quantitative complement fixation with a panel of tumour extracts from surgical specimens, it was found that the antiserum gave positive complement fixation with all squamous-cell carcinoma extracts tested, and with some of the extracts from bronchogenic carcinomas of differing pathological types. The antiserum was essentially negative for pooled extracts from normal lung, liver and spleen but gave a weak positive reaction with an extract of pooled foetal lung tissue.


Partial purification of human colonic carcinoma cells by sedimentation.

We have purified epithelial cells from human colonic tumours by velocity sedimentation in an isokinetic density gradient of Ficoll in tissue culture medium. In frozen sections of colonic carcinoma, histochemically demonstrable N-acetyl-beta-D-glucosaminidase (HDAG) was observed primarily in epithelial cells. We used this enzyme as a histochemical marker of epithelial cells. Initial suspensions of cells from colonic tumours suspended with 0-25% trypsin contained an average of 24% of the nucleated cells with HDAG. In the purest fraction obtained from gradient centrifugations, an average of 74% of the nucleated cells contained HDAG. After centrifugation, the quarter of the density gradient which contained the most rapidly sedimenting cells was purified 2-4-fold over that in the initial suspension. Cells in this zone of the gradient also gave rise to colonies in soft agar. Cells from initial suspension resulted in 15-25% as many colonies of 7 or more cells in cultures inoculated with the same number of nucleated cells. For the most part, cells obtained from the other zones of the gradient did not give rise to colonies in soft agar.


The solubility of 85Krypton in the regenerating liver of the rat.

The accuracy of liver blood flow measurement using the 85Krypton clearance technique depends on the use of an appropriate value for the solubility of 85Kr in liver relative to blood (the partition coefficient, lambda). This factor was studied in the regenerating liver remnant of the rat after a 67% partial hepatectomy, in order to find the influence of the ensuing postoperative fatty infiltration of the liver. There was found to be a rapid increase in lambda from 0-95 in the normal liver to 1-52 in the remnant 7-5 h after operation, followed by a more gradual return to normal levels by 35 h. The results indicate an early increase in the fat content of the liver after 67% hepatectomy and demonstrate that liver blood flow calculated from 85Kr clearance measurements in the early stages of regeneration must take into account the changes in lambda during that time.


The synergistic effect of aspirin and dipyridamole upon platelet thrombi in living blood vessels.

In rabbits previously injected i.v. with alloxan, serial observations of platelet thrombus formation in response to topical adenosine diphosphate (ADP) at sites of electrical injuries in pial arteries have been made. Using this model we have studied the effects of oral daily doses of dipyridamole (Persantin) and acetyl salicylic acid (ASA) upon platelet thrombus formation. Oral daily doses of 42 mg of ASA and 6 mg dipyridamole given separately in alloxan-treated rabbits are without effect. When given together orally, 42 mg and 6 mg respectively reduced the level of sensitivity to ADP for producing platelet thrombi to that established for the rabbits before the injection of alloxan. But withdrawal of these combined doses of dipyridamole and ASA caused the sensitivity of ADP for platelet thrombus formation to be raised to the much increased level present in rabbits soon after they are given i.v. alloxan. This apparent synergistic behaviour displayed by dipyridamole and ASA in these rabbits results in antithrombotic effects which are clearly absent when these two agents are given separately. It is of interest that the dose levels used here are equivalent, an a body weight ratio, to those being used in man in the current Persantin-Aspirin Reinfarction Study.


Influenza viruses and staphylococci in vitro: some interactions with polymorphonuclear leucocytes and epithelial cells.

Bacterial infection contributes substantially to the morbidity and mortality of human influenza. In vitro experiments were performed to test two hypotheses regarding a possible relationship between the virus and bacterial infection. Firstly, maintenance media from tissue and organ cultures infected with influenza virus were tested for the presence of staphylococcal growth-promoting factors; no evidence for these was found. Secondly, we looked for a virus effect on polymorphonuclear leucocyte function. We found that human leucocytes purified from venous blood and exposed to influenza virus responded normally to stimulation of hexose monophosphate shunt activity and chemiluminescence. However, their responses in tests of phagocytic function and of chemotaxis were inhibited. By various criteria this effect was specific to the virus and could be obtained even when only a few virus particles were present per leucocyte. We propose that this is a mechanism by which influenza virus could enhance susceptibility to bacterial infection in the lung.


Ultrastructure of failing myocardium due to induced chronic mitral insufficiency in dogs.

Left ventricular failure was produced in dogs by inducing mitral insufficiency and the cardiac muscle was examined for ultrastructural changes in thsese failing hearts after 5-10 months of mitral insufficiency. The left ventricular failure was established by haemodynamic measurements, chest X-ray and examination of the heart. In the failing heart, the increased number of mitochondria showed close approximation with the sarcolemmal membrane in the T-tubules as well as in the intercalated discs (ID); this is in contrast to what is seen in normal hearts, where T-tubules were mostly coupled with sarcoplasmic reticulum. It is possible that in the heart failing on account of mitral insufficiency mitochondria may be taking over the function of the sarcoplasmic reticulum. Although ID were jumbled up in the failing heart, the intercellular gap and specialized membrane junctions (gap and tight junctions, desmosomes) were quite comparable to normal, indicating that intercellular communication at ID in this type of heart failure is probably maintained. Nuclear chromatin in the failing heart was condensed and lined the inner nuclear membrane. Microbodies with a single limiting membrane were frequent and so were lipofuscin granules. The latter could be an end product of degenerative mitochondria. Golgi bodies in the failing heart were also present in locations away from the nucleus.


Thymus dependence and independence of intestinal pathology in a Trichinella spiralis infection: a study in congenitally athymic (nude) mice.

The hypothesis that non-specific histopathological gut changes are thymus-dependent was tested in a helminth infection--the nematode Trichinella spiralis. The study was performed in congenitally athymic (nu/nu) mice and their thymus-bearing heterozygous litter-mates (+/mu). The non-specific histopathological changes of the small intestine were judged on villus/crypt ratio and mitotic index; for the specific (= immunological) reaction the number of pyroninophilic cells in the small intestine was used as criterion. T. spiralis induced non-specific histopathological reactions both in nu/nu and +/nu mice, whereas the number of pyroninophilic cells was only increased in +/nu mice. It was concluded that the immunological reaction was dependent on the immune status of the host, whereas the non-specific histopathological changes were not, i.e. they were thymus-independent.


The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic inflammation.

The paralelism between the capacity of various agents to elicit chronic inflammatory responses in vivo and to induce the selective release of lysosomal enzymes from cultures of mouse peritoneal macrophages in vitro is discussed. Zymosan elicits an intense inflammatory response when injected i.m. in mice. Chrysotile asbestos produces a response of a similar nature and intensity as is seen with zymosan, while injections of acid-leached asbestos and polystyrene latex are not followed by inflammation. It is also shown that zymosan and asbestos induce a dose-dependent increase in the total enzyme activity of an inflamed muscle. On the other hand latex and acid-leached asbestos caused no significant increases in lysosomal enzyme levels. Agents eliciting inflammatory responses, such as zymosan and chrysotile asbestos induce a selective release of acid hydrolases from cultured macrophages; in contrast agents lacking the capacity to induce inflammation, such as latex and acid-leached chrysotile asbestos, do not induce the release of lysosomal enzymes from cultured macrophages.


Rapid blister formation in human skin with ammonium hydroxide.

The topical application to human skin of a 1:1 aqueous solution of ammonium hydroxide in a well drilled into a plastic block will provoke an intra-epidermal blister in an average time of about 13 min. The blister roof can be used for physico-chemical analyses of the horny layer while the base is suitable for studies of wound healing, bacterial infections, etc. The minimal blistering time (MBT) increases directly as the number of cell layers of the stratum corneum and ranges from 3 to 57 min in different regions and persons. The intensity of the dermatitis provoked by a 24 h exposure to sodium lauryl sulphate is strongly correlated with the MBT. The latter is therefore a reliable measure of cutaneous irritability. The blisters are virtually painless. The inflammatory reaction clinically and histologically is slight. Healing is rapid without scarring.


A study of oil of bergamot and its importance as a phototoxic agent. I. Characterization and quantification of the photoactive component.

It is important in the technique of photopatch testing, using oil of bergamot, to have determined the concentration of the active psoralen, bergapten, so as to avoid false negative responses in the assessment of phototoxic reactions. Techniques for assessing the phototoxic components of oil of bergamot are described and quantitative analyses of bergapten, the only significant photoactive compound in the samples examined, are reported. The phototoxicity of bergapten was found to be nearly the same as that of xanthotoxin (8-MOP) in tests on human skin.


The staphylococcal scalded skin syndrome. An experimental histochemical and electron microscopic study.

Histochemical and electron microscopic studies were carried out on the newborn mouse model of the staphylococcal scalded skin syndrome to investigate the mechanism of action of the staphylococcal epidermolytic toxin that causes it. Histochemical studies showed that an intra-epidermal split develops below the subcorneal zone which is rich in catabolic enzymes (the so-called esterase-acid phosphatase-rich band). However, histochemical alterations in the enzyme pattern could not be demonstrated. The earliest change revealed by electron microscopy was a widening of the intercellular space, with the formation of microvilli at the level between the stratum spinosum and stratum granulosum where the split later occurs. A clearing of the peripheral cytoplasm along the cell membranes was also revealed. In pre-split areas, adhesion between cell membranes of adjacent cells seems to be lost; desmosomes continue to hold the cells together but the split develops when these are broken by mechanical pressure. Later, damaged cell membranes may be seen. Extracellular keratinosomes remain unchanged. Although these findings do not agree with the already divergent results of other studies, they help support the findings of all groups that cases of the Lyell syndrome produced by staphylococci do not occur through necrolysis; it is therefore inappropriate to continue applying the term 'toxic epidermal necrolysis' to such cases.


The measurement of the cell cycle time in squamous epithelium using the metaphase arrest technique with vincristine.

In squamous epithelia with a single layer of germinative cells, the age distribution of cells in the cell cycle is shown to depend on the direction of the mitotic axis (i.e. a line joining the nuclei of daughter cells) relative to the plane of the basal layer. When axes are in the plane of the basal layer the age distribution is exponential; when cells divide at right angles to the plane of the basal layer, the age distribution is rectangular. When there is a ratio of vertical to horizontal axes, the age distribution is intermediate but can be calculated from knowledge of the proportion of axes in the plane of the layer. Squamous epithelia can be classified according to this arrangement of axes. When there are multiple layers of germinative cells, as in psoriasis, the age distribution is shown to be exponential to a good approximation, whatever the direction of the mitotic axes in the several layers. The importance of these observations is demonstrated by analysing metaphase arrest experiments with vincristine in the single layer of germinative cells in the mouse oesophagus, and in the several layers found in psoriatic epidermis. Choice of the wrong age distribution leads to an error of 6 h in the oesophagus and 23 h in psoriatic epidermis, when the mean cell cycle time is calculated. It is concluded that, in squamous epithelium, it is most important to know the age distribution before calculating the cell cycle time by methods involving measurement of the rate of entry of cells into mitosis or DNA synthesis.


Epidermal 'turnover time'--a new examination.

A new model for assaying epidermal cell turnover times is presented. It is based on desquamation rates of the stratum corneum and the consequent obligatory turnover time of the keratinocyte layer. A total epidermal turnover time of 45 days is derived from the model for the human volar forearms.


Antarctic environment and nail growth.

Nail growth of all fingers was measured on 13 men wintering in Antarctica. A mean rate of 109-5 micrometer/day was found with the longer digits having faster growth. No significant difference was demonstrated between the warmer and colder months of the study period. Monthly variations suggested that subjects had an individual rate irrespective of environmental influences. Comparison with previous studies both in polar and temperature conditions showed growth rates in Antarctica have increased progressively; present values being comparable with observations in temperate climates.


Drug-induced changes in the plasma membrane of Microsporum canis. A preliminary freeze--fracture study.

Commercial solutions of clotrimazole, tolnaftate and tolcyclate were tested for 12 h in cultures of Microsporum canis. They induced modifications in particle distribution, a blebbing of particle-free areas and the appearance of lamellar figures on the plasma membrane of fungus cells. The first two changes in the plasma membrane might be ascribed to a modification of the spectrin-like meshwork, while the third could be the result of a crystalline organization of membrane lipids.


Preponderance of lysosomal bodies in cultured fibroblasts from patients with recessive epidermolysis bullosa dystrophica. An electron microscopic study.

Fibroblasts of skin explants from three normal men and six patients with recessive epidermolysis bullosa dystrophica (EBD-R) were cultured in Dulbecco's medium, grown to confluence, sectioned and studied with the electron microscope. The normal control fibroblasts from the 6th to 13th passage (secretory phase) showed irregular or lobed nuclei with centrally scattered chromatin. They also had prominent RER, Golgi complexes, variously shaped mitochondria and cytoskeletal microfibrils. Their peripheral cytoplasm exhibited many vacuoles and a small number of these were autophagic lysosomes. In addition to the ultrastructural features described in the control fibroblasts, the EBD-R cells from the 6th passage contained remarkable numbers of strongly electron dense lysosomal bodies through their entire cytoplasm with very few empty vacuoles. It is speculated that the accumulation of these lysosomes may be connected with a primary metabolic cellular defect in the dermal fibroblasts of patients with EBD-R akin to that described in mucopolysaccharide storage diseases.


Failure of prostaglandins, prostaglandin metabolites and arachidonic acid to elicit chemotaxis of human polymorphonuclear leukocytes.

This paper reports chemotactic studies on human polymorphonuclear leukocytes using prostaglandins, prostaglandin precursors and prostaglandin metabolites in vitro. Chemotaxis could not be demonstrated when arachidonic acid, prostaglandins D2, E1, E2, F2alpha, and the prostaglandin metabolites 15 keto E2, 15 keto F2alpha were incubated with polymorphonuclear leukocytes using the Boyden millipore technique.


Phenothiazine therapy and plasma immunoreactive beta-MSH in schizophrenia and pruritic dermatoses.

Plasma immunoreactive beta-melanocyte-stimulating hormone (beta-MSH) concentrations were normal in schizophrenic patients on prolonged and high dosage phenothiazine therapy. A group of patients treated with chlorpromazine 25 mg three times daily for pruritic dermatoses also showed no significant change in plasma beta-MSH concentration.


Trichilemmal cysts arising in an extensive comedo naevus.

A 25-year-old male is described who had extensive linear comedo naevi present from birth, involving the face, both sides of the trunk, both arms, one palm, both legs and one sole. Within these lesions multiple trichilemmal cysts were arising giving rise to a zosteriform pattern of skin nodules. Both lesions were confirmed histologically. It is suggested that comedo naevus is a hamartomatous abnormality of the hair follicle in which all layers, including the external root sheath, are involved and from which trichilemmal cysts may arise.


Hereditary coproporphyria presenting with photosensitivity induced by the contraceptive pill.

A 26-year-old woman developed photosensitivity and jaundice after starting on an oral contraceptive agent. She was found to have hereditary coproporphyria. Histological examination of two liver biopsies taken during and after the acute attack did not reveal any changes thought to be due to hereditary coproporphyria. Screening of the patient's family revealed a further six latent cases.


Intestinal lymphoma complicating dermatitis herpetiformis.

A case is reported of a patient with dermatitis herpetiformis who has developed an intestinal lymphoma and a bladder carcinoma during the course of his illness. When considered in conjunction with three recently reported cases it is suggested that intestinal lymphoma may complicate the enteropathy of dermatitis herpetiformis.


Oriented fibrin crystallization: A phenomenon of hypersensitivity to bacteria in psoriasis, vasculitis and other dermatoses.

Heparinized blood from patients with a variety of dermatological problems was incubated with killed bacteria, bacterial extracts or Gram-negative bacterial endotoxin. Within 18-24 h asteroid bodies consisting of an amorphous centre with fine radiating needle crystals were seen. These bodies, not found in the blood of healthy volunteers, were most consistently observed in blood from patients with psoriasis, vasculitis and bacterial infections. Immunofluorescent studies disclosed the asteroid formations to be crystals of fibrin radiating presumably from a central platelet aggregate. The failure to demonstrate IgG, A, M or D suggests that the phenomenon results from the bacterial activation of complement by a non-immune yet specific pathway which in turn involves white cells, platelet aggregation and release of procoagulants.


Photochemotherapy in the treatment of psoriasis.

This article describes the satisfactory clinical improvement obtained in the majority of a group of 72 patients with psoriasis of various types as a result of the oral and/or topical administration of 8-methoxypsoralen followed by long wavelength ultraviolet irradiation. The irradiation source used was that of conventional longwave UV fluorescent tubes mounted in a specially constructed cubicle. Until such time as the long term effect of this form of photochemotherapy on the cell has been evaluated and the most appropriate regime worked out, it would seem to be important to restrict the amount of irradiation used to that required to produce acceptable maintained clinical improvement.


Novel techniques for the estimation of intracorneal cohesion in vivo.

Desquamation is the result of loss of cohesion between horny squames. This study is concerned with the in vivo measurement of intracorneal cohesion using three new techniques. A new instrument, the cohesograph, directly measures the force (g) required to distract a known area of partial thickness of stratum corneum in vivo. Sex and site differences were detected with this method. A surfometer was employed to measure the surface contours of the internal face of skin surface biopsies and when this measurement of the  surface irregularity was compared to the 'cohesograph' reading for  the same sites in 16 normal individuals a significant positive correlation of r=0-79 was found between the two sets of results. It is therefore suggested that the surfometer provides indirect measure of horny layer cohesion. Desquamation has also been estimated by using a modified 'scrub technique'. The scrub apparatus used is able to deliver a controlled stimulus to  the skin surface to release horny cells. The light absorbance at 400 nm of corneocyte suspensions was measured and found to correlate well (r=0-96) with the numbers of squames released. It is suggested that the three techniques used in conjunction provide a profile of stratum corneum cohesion in vivo.


The spatial correlation of fluctuations of the blood flow in forearm skin.

The oxygen tension at the skin surface, with the atmospheric oxygen supply excluded, may be measured polarographically on the human forearm. Under suitable environmental conditions, spontaneous fluctuations in skin surface oxygen tension can be recorded and these are the result of fluctuating blood flow in the superficial skin vessels. An array of separate cathodes in a single polarographic electrode assembly has been used to measure the fluctuations in  blood flow which are occurring simultaneously at seven different points in the skin. Spectral analysis of a long recording of such fluctuations shows that most of the power is concentrated at the lower frequencies but does not reveal any clearly defined dominant frequency. It is clear, however, from inspection of the fluctuation patterns, that recurring bursts of activity occur with quite well-defined periodicities in the range of 30s to 5 min. There is a stronger correlation between the fluctuations occurring at points on the skin surface less than 1 mm apart than between points further apart, although there are clearly some components which are common to points separated by up to 5 mm which was the largest separation of cathodes used in these experiments. These observations are supported by the value of cross correlation coefficients between the channels. These results suggest that the observed fluctuations are the result of at least two factors. The first one is common to all the channels but the effect of this may be overridden by a second and more local one controlling the blood flow.


Digital ischaemia due to vascular anomalies.

Four patients presenting with painful persistent cyanosis or gangrene of the fingers were found to have anomalies of arterial circulation of the hands and fingers. Investigations for systemic disease were negative. It is postulated that variations in the normal arterial anatomy predispose to digital ischaemia and that trauma, the contraceptive pill or infection may precipitate small thromboses and give rise to clinical ischaemia. Angiography should be undertaken in all patients presenting with persistent ischaemia of the fingers and toes, when the peripheral pulses are present and systemic disease has been excluded.


Scanning electron microscopy of hair. Observations on surface morphology with respect to site, sex and age in man.

The cuticular scale pattern of adult human terminal hair sampled from  10 different body sites was examined by scanning electron microscopy and showed: (1) differences according to site, the size of the cuticular scales being significantly greater in scalp hair than in hair taken from the nine other sites; (2) differences according to sex, the size of cuticular scales of facial, axillary and abdominal hairs being significantly larger in females; and (3) differences according to age, the size of cuticular scales from scalp hairs being significantly smaller in older than younger people.


Acrokeratosis verruciformis: (Hopf)--A clinical entity?

Contrary to the unitarian concept of acrokeratosis verruciformis and Darier's disease, a comparative familial, clinical and histopathological analysis of six cases each of these two diseases has suggested that they are separate entities. Though clinically similar, acrokeratosis remained non-dyskeratotic throughout life, whereas the acral lesions of Darier's disease showed, on careful scrutiny and follow-up, various gradations of benign acantholytic dyskeratosis. Malignant transformation indicated that dyskeratosis in Hopf's disease would be very rare and of a different nature. The probability of a genetic linkage between the two genodermatoses is reviewed and discussed.


Cross-striated banded structures in cutaneous leishmaniasis.

Banded structures were observed in 4 cases of cutaneous leishmaniasis. These structures were found in proximity to macrophages containing leishmania and were intermingled with native collagen, elastic fibres and ground substance fibrils. The possibility that banded structures are an indication of active, accelerated collagen production is discussed.


Hepato-erythropoietic porphyria presenting as scleroderma and acrosclerosis in a sibling pair.

Clinical and biochemical data are reported on a sibling pair with clinical and biochemical features of both erythropoietic protoporphyria and hepatic cutaneous porphyria. After many years of photosensitivity the clinical picture resembles systemic sclerosis.


Sarcoid granulomas of the skin produced by acrylic and nylon fibres.

The introduction into the skin of organic or inorganic substances can produce sarcoid-like granulomas. Two new granulomas of this type are described related to acrylic and nylon fibres. The aetiological diagnosis of such lesions can be confirmed by the identification of these synthetic materials within the-granuloma cells, using histochemical techniques used in the textile industry. An 'individual factor', probably immunological in nature, may be implicated.


Non-venereal sclerosing lymphangitis of the penis following herpes progenitalis.

Two patients are described in which non-venereal sclerosing lymphangitis of the penis occurred immediately after a herpes simplex infection. The possibility of a causal relationship between these two conditions is discussed.


Haemophilia treatment in the United Kingdom from 1969 to 1974.

A study has been made by the Haemophilia Centre Directors of the United Kingdom and Northern Ireland. From 1969 to 1974 2600 patients with haemophilia A and 388 with haemophilia B attended Haemophilia Centres for treatment. Of these patients, 71 are known to have died in the survey period. A record is presented of the amounts and types of therapeutic materials used each year during this time. The incidenceof jaundice and anti-factor VIII and anti-factor IX antibodies was recorded.


Defibrination of normal human blood in vitro: a method giving a high recovery of untraumatized cells.

A new automatic apparatus is described for the defibrination of blood in vitro at laboratory temperature which results in only small (less than 10%) losses of white cells. Freshly-drawn blood is mixed smoothly at high speed (greater than 1200 rpm) and fibrin is removed rapidly as formed. The apparatus is designed to produce minimum mechanical trauma to the blood. Subsequent in vitro incubation of red cells, granulocytes and lymphocytes demonostrated their viability to be comparable with cells obtained by other methods of defibrination.


Red cell metabolic and membrane features in haemolytic anaemia of alcoholic liver disease (Zieve's syndrome).

Zieve's syndrome (ZS), which consists of transient haemolytic anaemia, jaundice, hyperlipoproteinaemia, and alcohol-induced liver disease, was studied in male patients during the acute (n = 20) and the remittent (n = 10) phase. Chronic alcoholics (n = 10) without haemolysis and healthy male persons (n = 10) served as controls. Erythrocytes were separated into old and young cells by means of density-layer centrifugation. Those fractions which contained older red cells disclosed a pyruvate-kinase instability which resulted in impaired metabolism. Changes in membrane lipid composition as indicated by increased cholesterol and polyunsaturated fatty acids (PUFA) were also detected in patients during the acute phase of ZS. Alcohol-induced red-cell vitamin-E deficiency with a decrease in PUFA levels may provoke an oxidation of reduced red-cell glutathione which in turn results in the enzyme instability. This study lends further support to the hypothesis that the putative role of the red-cell metabolic injury in the origin of haemolysis in ZS cannot be envisaged without introducing membrane-linked and extracellular cofactors.


The correlation of cold agglutinin titrations in saline and albumin with haemolytic anaemia.

Cold agglutinin syndrome (CAS) is usually associated with IgM cold agglutinins with titres exceeding 1000 at 4 degrees C and a thermal amplitude of 30-32 degrees C. Occasionally patients are encountered who although having clinical and laboratory findings compatible with CAS do not have the characteristic serological findings. Thirty-two patients with a positive direct antiglobulin test due to complement sensitization were studied. Thirty-one of these patients had cold agglutinin titres greater than 64. Twenty-eight had haemolytic anaemia, including one patient with a cold agglutinin titre of only 8 against saline-suspended red cells. 53.6% of sera from patients with haemolytic anaemia reacted at 30 degrees C and 7.1% at 37 degrees C when albumin was not present, whereas in the presence of albumin all of the sera reacted at 30 degrees C and 67.9% reacted at 37 degrees C. None of the four patients without haemolytic anaemia reacted at 30 degrees C or 37 degrees C in the presence of albumin, even though one serum reacted to a titre of 1280 at 4 degrees C. Cold agglutinin titres and thermal amplitudes in the presence of bovine albumin were found to correlate better with haemolytic anaemia than reactions without albumin. If bovine albumin is utilized in compatibility testing, multiple cold autoabsorptions may be necessary before alloantibody activity at 37 degrees C can be excluded.


Effect of testosterone and oestradiol on erythropoietin production in vitro.

The effects of testosterone and oestradiol on erythropoietin production by mouse fetal liver in primary culture was studied. No stimulatory effect on in vitro erythropoietin production was observed by any of the oestradiol concentrations employed [10(-10)M to 10(-6)M]: whereas testosterone, only over a dose range of 10(-12)M to 10(-10)M, stimulated erythropoietin production by mouse fetal liver in culture. In addition, a stimulatory effect of testosterone on fetal liver tissue was obtained by injecting testosterone (20 mg/mouse) intramuscularly into pregnant mice 4 d prior to obtaining the fetal liver tissue for culture. Therefore, it is concluded that testosterone can exert a direct stimulatory effect on erythropoietin production by mouse fetal liver.


An investigation into the development and fate of neutrophil giant metamyelocytes using the techniques of electron microscopy and high resolution autoradiography.

The neutrophil giant metamyelocytes present in vitamin B12-and folate-deficient patients were studied using the techniques of electron microscopy and electron microscope autoradiography. The ultrastructural features of the cytoplasm of a proportion of these cells resembled those of promyelocytes and myelocytes, particularly with respect to the types of neutrophil granules present. This finding suggests that the giant metamyelocytes result from an abnormal type of development in promyelocytes and myelocytes which have been arrested or retarded in their progress through the cell cycle. The hypothesis that giant metamyelocytes eventually die within the marrow was supported by the observations that a significant proportion of these cells contain intracytoplasmic autophagic vacuoles, that some giant metamyelocytes suffer from a marked depression of RNA and protein synthesis and that degenerating giant metamyelocytes can be recognized within the cytoplasm of some bone marrow macrophages.


Assay and characterization of the factor in porcine and bovine plasma which aggregates human platelets.

A sensitive and objective bioassay has been developed to measure the factor present in porcine or bovine plasma which aggregates human blood platelets. The technique is based on direct measurement of platelet aggregation using an electronic particle counter. Using this assay it has been established that platelet aggregating activity is present in both bovine and porcine plasma and in therapeutic concentrates of factor VIII prepared from these materials. Platelet aggregating activity was found to be a function of the factor-VIII-related antigen concentration and independent of factor-VIII coagulant activity. The activity is absent in the plasma from pigs with von Willebrand's disease. It is concluded that factor-VIII-related antigen and the platelet aggregating factor are closely related and may represent one protein species.


A CRM-Positive variant of factor-VII deficiency and the detection of heterozygotes with the assay of factor-like antigen.

Nine patients with severe factor-VII deficiency, belonging to seven pedigrees were studied for the presence of factor-VII-CRM with an inhibitor neutralization assay. The antibody, raised in rabbits, did not precipitate the antigen and could only be used in a fluid phase assay to measure the capacity of plasma to neutralize inhibitory activity directed against factor-VII activity. In one of these nine patients normal amounts of factor-VII-CRM could be demonstrated. The CRM + patient did not show a clinical picture at variance with that of the CRM-patients. The investigation into this CRM+ pedigree revealed heterozygosity in nine out of 12 persons when using the ratio between biological factor-VII activity and factor-VII-CRM as the criterion.


HLA antigens in Addisonian pernicious anaemia: absence of a HLA and disease association.

An examination of HLA antigens in 72 unrelated Caucasian subjects with pernicious anaemia (PA) has revealed no significant association of any HLA-A or B genes with the disease. These data do not confirm the previous reports in the literature which had suggested an increased frequency of the B7 and/or A3 antigen among patients. In addition, the study of four families, each with two or more PA patients, does not support close linkage between disease susceptibility or autoantibody formation and the HLA locus. These data suggest that genes in or near the HLA region may not significantly affect susceptibility to PA.


Reversible C3 hypocomplementaemia in megaloblastic anaemia due to vitamin B12 deficiency.

Serum C3 and C4 levels have been determined in patients with Addisonian pernicious anaemia (PA) and megaloblastic anaemia due to vitamin B12 deficiency from other causes, before and after treatment, in order to study the interaction between vitamin B12 deficiency and complement and the role of complement in the pathogenesis of the gastric lesion of PA. C3 levels are significantly reduced in vitamin B12 deficiency and return to normal on treatment; C3 levels correlate with the degree of anaemia but not with serum vitamin B12 levels at diagnosis. C4 levels are normal. These observations suggest that the observed C3 hypocomplementaemia is not a consequence of immune mechanisms, but may be due to altered synthesis of C3 complement component.


Erythroid hypoplasia in myelofibrosis: a feature associated with blastic transformation.

Four cases of myelofibrosis have shown a pattern which is usually found only where there is erythroid hypoplasia and in none of these was there evidence of extramedullary erythropoiesis. Three of these cases terminated in a blastic phase. The findings suggest that the occurrence of erythroid hypoplasia in myelofibrosis may be associated with blastic transformation--whether as a predisposing factor or as a secondary event is still speculative. This phenomenon is discussed in relation to the natural history of myelofibrosis.


Adenosine deaminase (ADA) activity in lymphocytes of normal individuals and patients with chronic lymphatic leukaemia.

Adenosine deaminase (adenosine aminophydrolase, ADA) activity was found to be low in lymphocytes of chronic lymphatic leukaemia (CLL) patients compared to normal lymphocytes. This was determined on 42 controls and 49 CLL patients. The mean activity in normal lymphocytes was found to be 4.35 +/- 3.34 mumol/h/10(8) cells while in CLL cells it was 2.45 +/- 2.54 mumol/h/10(8) cells.


Evidence that stimulation of megakaryocytopoiesis by low dose vincristine results from an effect on platelets.

Appropriate low dosages of vincristine stimulate megakaryocytopoiesis and produce thrombocytosis. In this study of the thrombocytotic action of vincristine, administration of a single dose of 0.1 mg/kg to rats produced an increase in megakaryocyte concentration, diameter and 24 h [3H]thymidine labelling index. Transfusion of one body equivalent of platelets from normal donors prevented stimulation of megakaryocytopoiesis by vincristine whereas platelets from vincristine-treated donors did not. These results suggest that vincristine stimulates megakaryocytopoiesis by altering the functional role of circulating platelets in the regulation of thrombopoiesis.


Comparison of haematological features of the beta0 and beta+ thalassaemia traits in Jamaican Negroes.

Haematological characteristics have been compared in 29 subjects with heterozygous beta0 thalassaemia and in 33 subjects with heterozygous beta+ thalassaemia, identified by the type of sickle cell-beta thalassaemia among close relatives, in a Jamaican Negro population. Total haemoglobin, MCV and MCH were significantly lower in the beta0 type but the level of Hb A2 was not significantly different. Individual values for MCV, MCH and Hb A2 in the beta+ type occasionally overlapped those in the normal population casting doubt on the adequacy of these criteria in identifying all cases of heterozygous beta+ thalassaemia. The haematological differences are those which would be expected on theoretical grounds. The inability to confidently differentiate the two types of heterozygous beta thalassaemia has implications for genetic counselling. The inability to distinguish heterozygous beta+ thalassaemia from normals on any single haematological index suggests that surveys depending on estimations of Hb A2 or on MCV alone may have underestimated the prevalence of the beta+ thalassaemia gene.


Reduced ferrochelatase activity: a defect common to porphyria variegata and protoporphyria.

Erythroid ferrochelatase activity has been studied in the normoblasts of patients with porphyria variegata and protoporphyria. Two methods were used for the investigation: one using intact cells and the other lysed cells, each measuring the amount of haem synthesized by normoblasts. In patients with porphyria variegata, ferrochelatase activity estimated by both methods was approximately 50% of the normal, and in protoporphyria the ferrochelatase activity was normal in intact normoblasts but was 20% of the normal in sonicated normoblasts (marrow lysates). It is suggested therefore that in porphyria variegata a dominantly inherited structural gene mutation results in an active ferrochelatase whereas in protoporphyria the genetic mutation results in an unstable ferrochelatase. The mechanism of the enzyme instability is not known though a number of postulates are discussed.


Cobalamin dependent methionine synthesis and methyl-folate-trap in human vitamin B12 deficiency.

The activity of methionine synthetase (MS) is important for the rapid growth of human haematopoietic cells and cultured lymphoblastoid cells. The MS reaction is the only known metabolic step in which both vitamin B12 and folate are essential in a single enzyme reaction. In vitamin B12 deficiency the MS activity in bone marrow cells is significantly lower than that in normal bone marrow. Free tetrahydrofolic acid (H4PteGlu) is normally liberated from its metabolically inactive storage form, 5-methyl-H4PteGlu (CH3H4PteGlu), in the cobalamin-dependent MS reaction. Thus, in vitamin B12 deficiency H4PteGlu is not available in sufficient concentration to maintain the de novo synthesis of thymidylate and purines, and accords with the methyl-folate-trap hypothesis. After treatment with amethopterin (Methotrexate), the incorporation of 3H-deoxyuridine into cellular DNA is reduced. In proliferating normal cells this effect of methotrexate can be prevented (and the cells rescued) with CH3-H4PteGlu or with CHO-H4PteGlu (5-formyl-H4PteGlu; Leucovorin). On the other hand, in vitamin B12 deficient bone marrow cells this so-called rescue-effect could only be achieved with CHO-H4PteGlu and not with CH3-H4PteGlu. These observations also support the hypothesis of the methyl-folate-trap in vitamin B12 deficiency. Decreased MS activity in vitamin B12 deficiency seems to be the essential metabolic fault, which is responsible for secondary alterations of folate metabolims. Thus, measurement of MS activity may allow direct functional assessment of vitamin B12 deficiency, at least with regard to DNA metabolism.


Characterization of serum ferritin in iron overload: possible identity to natural apoferritin.

Serum ferritins from a patient with haemochromatosis and from a patient with transfusional siderosis were compared with tissue isoferritins on the basis of their iron content, isoferritin spectrum and immunological properties. Both serum ferritins had a low iron content and corresponded to only the most basic isoferritins in liver. The serum ferritins were very similar to the natural apoferritin from liver in all respects.


Intracellular iron transport in rat intestinal epithelium: biochemical and ultrastructural observations.

Iron absorption by the rat intestinal epithelial cell has been studied by differential centrifugation of mucosal homogenates and by electron microscopic autoradiography. Autoradiography of both subcellular pellets and whole gut confirmed the biochemical findings. Mitochondria play a quantitatively significant role in iron metabolism within the epithelial cell but do not take part in the transport of iron across the cell during iron absorption.


Haematological changes associated with the McLeod phenotype of the Kell blood group system.

The McLeod phenotype is inherited as an X-linked characteristic. The red cells have weak antigenicity in the Kell blood group and lack Kx, a precursor-like substance that appears to be necessary for proper biosynthesis of Kell antigens. Kx antigen is also required for establishment of normal cell morphology. Absence of Kx antigen causes a membrane abnormality, in which the most prominent feature is acanthocytosis, and a compensated haemolytic state. The X-linked gene that determines normal Kx production is called X1k. Inheritance of a variant allele at the Xk locus is responsible for lack of Kx synthesis and the McLeod phenotype. The Xk locus is inactivated by the Lyon effect, and female carriers of the variant gene exhibit blood group mosaicism in the Kell system and have a dual red cell population of acanthocytes and discocytes.


Development of Neutrophilia by serially increasing doses of dexamethasone.

Dexamethasone (4-8 mg/m2 body surface area) was given orally or intravenously to six normal volunteers. The maximum neutrophil count occurred 4-6 h after oral or intravenous administration of dexamethasone and was due almost entirely to an increase in mature neutrophils; concomitantly there was a lymphocytopenia. A second rise in the neutrophil count occurred 24 h after oral ingestion of dexamethasone, coinciding with a lymphocytosis. Neutrophil alkaline phosphatase (NAP) activity during development fell as the neutrophil count rose. Other haematological values were unchanged except for small increments in erythrocyte sedimentation rate (ESR). Sodium concentration in serum and urine remained normal but urinary potassium excretion and urine volume increased after the intravenous dose. There was a direct relationship between plasma concentration of dexamethasone and the rise in neutrophil count following intravenous but not oral administration. The concentration of dexamethasone in plasma fell to half its peak value in 2-6 h. Dexamethasone-induced neutrophilia was similar to that induced by other corticosteroids. Dexamethasone in a dose of 6 mg/m2 produced minimal discomfort while inducing an adequate neutrophilia in the volunteers.


Metabolism and function of human platelets washed by albumin density gradient separation.

A method for washing platelets by albumin density gradient separation, originally designed for the study of platelet coagulant activities, has been modified for platelet aggregation and metabolic studies. Platelets are sedimented into a continuous density gradient of isosmolar albumin containing apyrase to protect them from clumping and physical injury and are resuspended in calcium-free Tyrode's solution. The mean recovery of platelets after two separations relative to platelet-rich plasma (PRP) was 90.3%. When small amounts of plasma were added to washed platelet suspensions, aggregation and release of [14C]5-hydroxytryptamine (5HT) in response to adenosine diphosphate (adp) or 5HT were similar to results obtained with PRP. When fibrinogen was substituted for plasma, ADP-induced aggregation occurred but was feeble. Without added plasma or fibrinogen, platelets were refractory to ADP and insensitive to the cyclic endoperoxide analogue U44619. When both ADP and U44619 were added simultaneously, in low concentrations, to washed platelets without added plasma or fibrinogen, aggregation occurred immediately. Washed platelets were not aggregated by adrenaline, which potentiated ADP-induced aggregation. Several biochemical measurements which are sensitive indicators of cellular damage were normal in washed platelets, including [14C]adenine uptake, adenylate energy charge, hypoxanthine formation and the response of adenylate cyclase to stimulation by PGE1 or PGD2. Platelet coagulant activities were not made available and heparin-neutralizing activity (HNA) was not spontaneously released by the washing procedure, but the washed platelets responded normally to appropriate agents by developing coagulant activities and releasing HNA. The ultrastructure of washed platelets was similar to those in control PRP. Inclusion of apyrase in the first albumin gradient had a beneficial effect on platelet morphology, aggregation and metabolism, but washing at 37degreesC compared with 25degreesC did not. Albumin density gradient separation is a useful method for isolating platelets for aggregation and metabolic studies.


Cancers of the lung and nasal sinuses in nickel workers: a reassessment of the period of risk.

Nine hundred and sixty-seven men who were employed in a nickel refinery in South Wales on at least two occasions five or more years apart before 1945 have been followed up, and the mortality rates from different causes related to the date of their first employment. Previous reports suggested that the occupational risks of lung and nasal sinus cancer had been eliminated by 1925. It is now shown that the risk persisted until 1930, which accords better with the temporal changes in the process.


Application of blood cadmium analysis to industry using an atomic fluorescence method.

A flame photometric method using atomic fluorescence (AFS) for cadmium (Cd) estimation is described and applied to the measurement of Cd in blood. The AFS system employs a modified, low cost atomic absorption spectrophotometer, with a high intensity Cd light source provided by an electrodeless discharge tube, excited in a thermostatted microwave cavity. The analytical sensitivity of the technique is sufficient to permit dilution (1 in 5) of blood, before aspiration into the air-hydrogen flame. The method is rapid (25 duplicates/hour), and gives acceptable precision (coefficient of variation within batch 2-5%, between batch 8-1%). The method was applied to a reference population and to three different groups of industrial workers. The reference population had a mean blood concentration of 35-1 nmol Cd/litre. Group 1 (general categories of worker) had 65-2 nmol Cd/1, Group 2 (demolition workers), 137-9 nmol Cd/1, and Group 3 (shipbreakers), 105-9 nmol Cd/1. There was a relationship between increases in blood Cd and in blood Pb which was statistically significant for Group 3.


Occupational exposure to manganese.

The relationship between the degree of exposure and biological effects of manganese was studied in a group of 369 workers employed in the production of ferroalloys. Two other groups of workers, from an electrode plant and from an aluminium rolling mill, served as controls. Mean manganese concentrations at work places where ferroalloys were produced varied from 0-301 to 20-442 mg/m3. The exposure level of the two control groups was from 2 to 30 microgram/m3 and from 0-05 to 0-07 microgram/m3, in the electrode plant and rolling mill respectively. Sixty-two (16-8%) manganese alloy workers showed some signs of neurological impairment. These signs were noticeably less in the two control groups (5-8% and 0%) than in the occupationally exposed group. Subjective symptoms, which are nonspecific but may be symptoms of subclinical manganism, were not markedly different in the three groups. However, in the manganese alloy workers some of the subjective symptoms occurred more frequently in heavier smokers than in light smokers or nonsmokers. Heavier smokers engaged in manganese alloy production showed some of the subjective symptoms more often than heavier smokers from the control groups.


Antagonistic activity of poly (4-vinylpyridine-N-oxide) to the inhibition of viral interferon induction by asbestos fibres.

The depressive activity of both serpentine (Canadian and Rhodesian chrysotiles) and amphibole (amosite, crocidolite, and anthophyllite) asbestos fibres on interferon induction by influenza virus was significantly diminished or abolished completely when either asbestos fibres or LLC-MK2 cell monolayers were pretreated with poly(4-vinylpyridine-N-oxide). Maximal antagonistic activity of the polymer was time and concentration dependent. Pretreating asbestos fibres with the polymer was more rapid and effective in encouraging viral interferon synthesis than pretreating cell monolayers. Virus multiplication in the presence of asbestos fibre-treated cell monolayers attained a twofold higher level than that noted in normal cell monolayers or those containing polymer-pretreated asbestos fibres. These findings were related to the suppression of interferon production.


Acceptable levels for the breathing resistance of respiratory apparatus: results for men over the age of 45.

Tolerance of additional external resistance to inspiration has been investigated in a group of coalworkers older than 45 years. Peak inspiratory pressure, external respiratory work rate, ventilation, and gas exchange were measured, during periods with and without one of four inspiratory resistances, on 41 subjects walking on a treadmill. Minute volume was reduced, breathing frequency was unchanged and oxygen uptake and carbon dioxide elimination were reduced by the presence of resistance. It was established that, at the workload studied, older men were able to tolerate inspiratory resistance to at least the same extent as younger men, when the respiratory work was expressed in terms of unit ventilation. It is suggested that the acceptable level of breathing resistance established for younger men can also be applied to older workers.


Effects of fluorocarbon propellants on respiratory flow and ECG.

Ten subjects were exposed to the propellants freon 11, freon 12, freon 114, to two mixtures of freon 11 and 12 and to a mixture of freon 12 and 114. The length of exposure was 15, 45 or 60 seconds. Maximum expiratory flow-volume (MEF) curves and ECG were recorded before, and intermittently up to 1 hour after, exposure. Breathing level concentrations of propellants during exposure were determined by gas chromatography. All freons induced biphasic reduction of ventilatory capacity on inhalation. The first fall occurred within a few minutes of exposure while the second was delayed 13-30 minutes after exposure. The effects of mixtures were greater than those of individual freons. The relative fall in MEF 75% was more pronounced than that in MEF 50%. No clear-cut pathological changes in ECG were found. Nevertheless, most subjects developed variations in heart rate exceeding those noted before exposure. In a few cases inversion of the T wave, and in one case atrioventricular block, were observed.


Efficiency and daily work effort in sugar cane cutters.

Productivity (metric tons (tonnes)/day), efficiency (kg cane cut/litre Vo2), and effort (percent Vo2 max sustained during an 8-hour workday) have been measured in 54 Colombian sugar cane cutters. In workers who sustained less than 40% Vo2 max during the workday, the effort expended was related to productivity (4 = 0-71) but efficiency and productivity were not significantly correlated. In 16 workers sustaining a greater than 40% Vo2 max during the workday, productivity and effort were not related and efficiency was significantly reduced. Subjects using less than 40% Vo2 max were divided into good, average and poor producers and compared with the men with low efficiencies. In general, these inefficient men had the anthropometric and physical fitness characteristics of low productivity workers (smaller stature, weight and Vo2 max). However, the frequency of good, average, and poor cutters in the inefficient group did not differ from that of the men expending less than 40% of their maximum effort nor was their average productivity different. No obvious reasons for the differences in efficiency and effort of these men were found.


Screening for liver disease in vinyl chloride workers.

Following the occurrence of hepatic fibrosis and angiosarcoma in polyvinyl chloride autoclave workers, a screening programme was set up for workers at risk in a large production plant. There was no significant difference in liver function tests between workers and a control group of men in the same factory, not exposed to vinyl chloride. Four exposed workers out of 422 were found to have enlarged spleens compared with none out of 202 controls. Liver biopsies from selected cases showed no significant pathological changes, although there was minimal increase in portal tract and sinusoidal fibrosis in exposed workers.


Radiological assessment of small pneumoconiotic opacities.

Problems in the assessment of small opacities, within the ILO U/C International Classification of Radiographs of the Pneumoconioses (International Labour Office, 1972), are discussed in the light of readings by three experts of a group of films in which both rounded and irregular small opacities frequently coexisted. There was considerable disagreement on whether opacities were rounded or irregular, but reasonable agreement on type (diameter or thickness). As expected, rounded opacities were more commonly recorded in upper zones of the lung, and irregular opacities in lower zones. However, determination of which zones were affected left much to be desired. Perhaps as a result, major problems arose over the assessment of combined profusion.


Energy dispersive x-ray analysis in the study of pneumoconiosis.

Identification of inorganic substances in the lung is an important step towards the establishment of a cause and effect relationship in the study of pneumoconiosis. The conventional methods for this identification usually require an ashing which makes it difficult to study the localisation of these substances in relation to pathology. A method is described to identify foreign substances in the tissue obtained either on biopsy or autopsy without destroying them. The technique employs scanning electron microscopy together with energy dispersive x-ray analysis. This method not only allows simultaneous multi-elemental analysis of over 80 elements, but also permits detailed morphological examination while the tissue is being analysed.


A study of social problems in a group of young women treated with brief psychotherapy.

This paper reports on a series of young women with social problems treated with brief psychotherapy in a NHS setting and fulfilling difinite selection criteria. It is suggested that we have paid more attention to the role of the mother infancy and have tended to neglect the influence of the father. While we have studied emotional change in the growing child we have not perhaps made sufficient allowance for changes in parents. This study examines the role of the father in his daughter's adolescence. Awareness of this factor in the clinical setting might help to shorten the course of psychotherapy in appropriate cases. Sociologically it is relevant to our views on parenthood.


The organization of judgements based on positive and negative adjectives in the Bannister-Fransella Grid Test.

This study compared the level of organization of judgements involving evaluatively positive (E+) adjectives such as kind with that of judgements involving evaluatively negative (E-) adjectives such as stupid in the Bannister-Fransella Grid Test. The grids of 275 subjects, including 43 normals, 24 thought-disordered schizophrenics, 30 non-thought-disordered schizophrenics, 50 "mixed" schizophrenics, 18 depressives, 16 neurotics, and 94 undiagnosed new admissions were examined. The organization of judgements based on E+ ones across all ten groups. These results are inconsistent with the "null hypothesis" that the grids of thought-disordered schizophrenics contain only random "error variance" since they reveal a source of systematic variation in the grids of thought-disordered schizophrenics as well as those of other populations. These data were discussed also in relation to the hypothesis that comparative judgements involving E- adjectives are more difficult than those involving E+ ones.


The psychological gains and losses of religious conversion.

A presentation of case material demonstrating productive identify formation and conflict resolution resulting from religious conversion with at the same time significant repression that so affected personal relatedness as to eventually lead to breakdown of adjustment.


Systemic aspects of abstinence and addiction.

An examination of the addict in his social context reveals that an important aspect of abstinence is the transform of the problem of addiction from an aspect of the social system to within the addict. The drug subculture, the addict's family, and a methadone clinic all covertly elicit and reinforce this transformation maintained by the myth that the addict's is "out of control".


Psychogenic vertigo within an anxiety frame of reference: an experimental study.

The theoretical point of departure here was the assumption that a psychogenic vertigo patient displaces affect, or experience of anxiety to one of dizziness, the dizziness serving as an anxiety equivalent. This is seen to imply a change in the locus of experience from the me to the not-me sphere. "Percept-genetic" techniques and a spiral after-effect measurement were used to compare 23 patients with presumed psychogenic vertigo with a control group matched in sex, age, education and occupation. Results of the percept-genetic techniques showed the patients to display stronger signs of affect anxiety than subjects in the control group. Also two main subgroups of patients were differentiated with the help of the descriptive instruments, one group with signs of a primitive-hysteroid mode of functioning, the other with signs of an obsessive-compulsive mode. For both subgroups the suggested displacement mechanism seemed to be functioning. Its apparent effect differed, however, for the two subgroups: in the "primitive-hysteroid" group the displacement mechanism was more effective. The "obsessive-compulsive" group showed stronger signs of affect anxiety, dizziness here being better characterized as a concomitant than as an equivalent of anxiety. Results of a follow-up two years after the investigation also showed a poorer development of symptoms within the "obsessive-compulsive" group.


Sixteen months' experience with 140 posterior chamber intraocular lens implants.

Three main designs of posterior chamber lenses in 140 cases have been reviewed. The visual results are satisfactory; patient satisfaction is good; and postoperative complications are limited to anterior dislocation of the feet of the lens and the necessity to wash out cortical remnants from behind the prosthesis in a small percentage of cases. The posterior chamber prosthesis is free from some of the complications of other intraocular lenses and probably provides the most 'normal' looking eye of any pseudophakoi.


Technique of implantation of extrapupillary iris lens: 8 years of clinical experience.

A new type of intraocular lens has been devised. The lens is iris-supported but, in contrast to conventional iris-clip lenses, is fixed at the iris periphery, leaving the pupillary region free. The lens may be implanted either anterior or posterior to the iris plane. Implantation into the posterior chamber is particularly beneficial when combined with an extracapsular extraction. Eight years' experience (189 operations) underlines a number of important advantages of the extrapupillary iris lens. The pupil is not distorted, so that its form and function remain normal; the danger of dislocation is avoided; and the lens may be employed in the presence of an iris coloboma. The supporting prongs of the lens are made of gold and platinum alloys, which add considerably to its tissue tolerance. So far no complication has arisen necessitating removal of such a lens. This new type of intraocular lens offers a combination of efficacy, safety, and technical simplicity.


Aphakic macular oedema following prosthetic lens implantation.

Fluorescein angiography of the iris was performed on patients with plastic lens implants with cystoid oedema of the macula, and the nature of the vascular changes was compared with controls provided by patients who did not have macular disease. Densitometry was used to quantitate leakage of fluorescein dye into the anterior chamber in residual angiograms 5 minutes after injection. Cystoid oedema was associated with marked increase in vascular permeability of the iris in the patients with implants, and in aphakics without implants, but to a lesser degree. Although it cannot be concluded that implants themselves cause either the increase in permeability or the onset of macular oedema, the presence of such implants must be considered an additional hazard in an eye which is already at risk. Iris angiography can be used as a diagnostic aid in patients in whom macular oedema is suspected. A persistent increase in permeability associated with a reduction in visual acuity should act as a warning of further visual loss and of eventual cystoid macular degeneration.


Posterior dislocation of an intraocular lens implant and its removal.

The cause of dislocation of an intraocular lens is a direct blow or jerk, and dislocation may complicate both iris-supported and capsule-supported lenses. In capsule-supported lenses the implant dislocates towards the anterior chamber but in iris-supported lenses the dislocation is posterior. A technique for removal of a posterity dislocated lens is described.


Pseudophakic pupillary-block glaucoma.

Four cases of iris-supported pseudophakic pupillary-block glaucoma were presented. Pupillary-block glaucoma is the first postoperative complication seen following the implantation of an intraocular lens, and in our series occurred at an incidence of 3-8%. A short review was made of pupillary-block glaucoma with all types of intraocular lenses, with emphasis on the iris-supported lens. The role of inflammation, haemorrhage, and vitreous and lens material in obstructing aqueous flow at the pupil and peripheral iridectomy site was emphasised. Pitfalls in the diagnosis and management of this condition were reviewed. Methods of prevention and treatment were reviewed with emphasis on early mydriasis, along with carbonic anhydrase inhibitors and hyperosmotic agents as a primary medical treatment. Iridectomy, laser iridotomy, or transfixation of the iris was mentioned as a surgical treatment.


Cataracts and avionic radiations.

Nine cases of hertzian radiation cataracts are reported among personnel working in operational aviation environments, where they were irradiated repeatedly at subliminal non-thermal field intensities. The resultant ocular pathology evolved insidiously and slowly over a period of years in a similar way to other forms of radiational injury. By the time of consultation examination, all had progressed to a relatively late state, exhibiting not only capsular cataract but also vesiculation and opacification of the proximal subcapsular lens substance. In addition to the ocular dangers of chronic exposure to nonionising radiation reference is made to the nonthermal effect or the radiation effect per se, as this could relate to general health--for example, as a possible previously unsuspected aetiological or contributory factor in many other disease processes.


Dilemma of the swollen optic disc: a fluorescein retinal angiography study.

In all of 100 consecutive patients referred for retinal angiography with a clinical diagnosis of probable or possible papilloedema a definite diagnosis was made from neurological assessment, neuroradiological investigations, and follow-up. The cases have been divided into 2 groups--those with proved papilloedema and those which have been called either normal or pseudopapilloedema. In all cases the retinal angiograms showed normal or increased optic disc vascularity and normal or increased early and late disc fluorescence. On the basis of these alone clear differences could be shown between the groups. All cases with papilloedema showed a combination of either excess late fluorescence with excess early fluorescence or excess late fluorescence with excess disc vascularity. Only 2 cases of pseudopapilloedema (both with optic disc drusen) showed this combination, and in both the pattern of disc fluorescence was different from that seen in papilloedema. Retinal angiography therefore seems to be of considerable value in differentiating true from pseudopapilloedema, though this is possible only when each stage of the angiogram is carefully studied.


Neoplasm of mixed mesenchymal and neuroepithelial origin of the optic nerve.

A case is reported of a 19-year-old male having right proptosis for 4 years because of a mixed meningioma and astrocytoma of the ipsilateral optic nerve. The sheath of this nerve is analogous to the leptomeninges, and neuroglial cells constitute the stroma of the nerve. Both meningioma and astrocytoma therefore can arise primarily in the optic nerve, and they may be combined in the same mass, forming a neoplasm of mixed mesenchymal and neuroepithelial origin.


Vasoformative properties of normal and hypoxic retinal tissue.

By cannulating the stroma of rabbit corneae, and introducing extracts of retina and vitreous from newborn kittens subjected to vaso-obliterative doses of oxygen, an attempt was made to test the hypothesis that ischaemic retinal tissue releases a factor with vasoformative properties. It was found that, although retino-vitreal extracts from the test animals elicited a positive response in just over half the experiments, the degree of corneal vascularisation provoked by extracts from intact control animals was only marginally less. Consequently our findings do not permit any definite answer regarding the existence of a specific factor responsible for the proliferation of new vessels on the retinal surface in states associated with retinal hypoxia.


Localisation of macrophage lysosomal enzyme in experimental toxoplasma retinitis.

Rabbit retinal tissue experimentally infected with Toxoplasma gondii was processed for the lysosomal enzyme aryl sulphatase. Abundant lysosomal activity was found in lysosomal bodies of the infected macrophages. There appeared to be a lack of fusion of the lysosomal bodies with the phagosomes containing the organisms. Examination of the majority of macrophage vacuoles containing trophozoites failed to show consistently lead sulphide deposition for aryl sulphatase activity. By light microscopy 83% of 115 macrophage vacuoles containing the trophozoites of T. gondii showed an absence of lysosomal enzyme activity; 7% of the vacuole containing the trophozoites were found to contain lysosomal enzyme activity. In the remaining 10% of the vacuoles containing the trophozoites of T. gondii the presence or absence of lysosomal enzyme activity could not be determined with certainty. The frequent absence of lysosomal enzyme activity within the phagosomes containing T. gondii organisms may be related to the parasite's ability to multiply and encyst in an intracellular locus. The abundant lysosomal enzyme activity in the lysosomal bodies within the cytoplasm of the infected macrophages may contribute to the cellular destruction of surrounding tissues when infected macrophages burst open owing to proliferation of the trophozoites.


Photoreceptor differentiation in retinoblastomas and its significance in prognosis.

Fleurette is an expression of photoreceptor differentiation and its presence is said to indicate a good prognosis. Twenty-four eyes from 22 cases of retinoblastoma sent to the Mitrani Foundation laboratory between the years 1964 and 1976 were reviewed histologically and clinically. The presence of differentiation in the tumour was not always associated with a good prognosis. The most important prognostic factor seemed to be the length of time the tumour is allowed to remain in the eye. The longer it remains the more undifferentiated the tumour cells become and the greater the probability that it will spread into the choroid and the optic nerve and out of the eye through the sclera and metastasise throughout the body. The presence of gliosis seems to improve the prognosis.


Comparison of ultrasonic and photographic methods of axial length measurements of the eye.

The axial length of 25 eyes was measured by the photographic method and by ultrasonography. The photographic measurements were consistently larger than the ultrasonic, but analysis gave a correlation coefficient of r = 0-8483. The results suggest that the centre of rotation of the eye lies posterior to the anatomical centre of the globe. Using an empirical method of calculation and allowing for an error of +/-0-3 mm in the ultrasonic measurement, the photographic results were within +/-0-5 mm in 13 eyes and +/-1-0 mm in 7 eyes. The photographic method may be helpful as a guide to the power of intraocular lens implants and for comparing axial lengths in population studies.


Prevalence of refractive errors in adults over 40: a survey of 8102 eyes.

The prevalence of refractive errors was studied in an adult rural population. Of the 8102 eyes studied 18-4% were myopic, 57-1% were emmetropic, and 24-5% were hypermetropic. Mild myopia was commoner in males than in females, and mild hypermetropia was commoner in females than in males. There was increasing hypermetropia with increasing age, probably due to unmasked, latent hypermetropia up to the age of 70 years and to a true shift toward hypermetropia after the age of 70 years.


Chlorpromazine induces population increase of synaptic vesicles in the rat hypothalamic ventromedial nucleus.

The population of synaptic vesicles per synaptic area in the hypothalamic ventromedial nucleus of rats treated with chlorpromazine (CP) for 3 days was compared with that of controls. In type I synapse, which contained 400-800 A small spherical vesicles (s-vesicles), together with 800-1200 A large spherical dense-cored vesicles (lc-vesicles), the population of s-vesicles increased 57.8% in the CP rats, In type II synapse, which contained only s-vesicles, the rate of increase among CP animals was 15.4%. Findings suggested that CP blocks the release of the vesicles from the presynaptic site or inhibits the transport function for biogenic amines through the presynaptic membrane, and type I synapse may be aminergic.


A family history study of schizo-affective disorder.

All patients with a discharged diagnosis of schizo-affective disorder (53 cases) admitted to the University of Iowa Department of Psychiatry during 1971-73, were selected for the present study. Schizophrenia (chronic psychotic disorders) and affective disorders (episodic remitting disorders with affective symptoms) were diagnosed among parents and sibs on the basis of chart material. The frequency of schizophrenia was 0.9%; the frequency of affective disorders, 11.8%. These results were compared to data for the relatives of cases of schizophrenia and affective disorders. There were no significant differences for the rates of schizophrenia among the relatives. The rate of affective disorder among the relatives of the schizo-affectives was significantly higher than for the relatives of schizophrenics (3.2%), and not significantly different from the relatives of affective disorder cases (8.3%). An analysis of outcome, precipitants, and age of admission also support the view that schizo-affective disorder should not be routinely classified as schizophrenia for research purposes.


Prostaglandin F in patients with primary affective disorder.

Two aspects of prostaglandin F (PGF) metabolism were assessed in patients with primary affective disorder. For a group of hospitalized patients cerebrospinal fluid PGF was measured by radioimmunoassay and the effects of probenecid and L-tryptophan were determined. For outpatients attending our Lithium Clinic, plasma PGF was measured and the acute and chronic effects of lithium were determined. The results of the studies reveal apparently normal concentrations of PGF in cerebrospinal fluid. These concentrations increase twofold after probenecid, indicating that PGF is transported out of the central nervous system by a probenecid-sensitive active transport system. Evidence for inhibition of PGF synthesis during L-tryptophan treatment was found. The results for outpatient plasma studies suggest no effect on PGF with 12 weeks of lithium treatment, although a slight elevation of plasma PGF with chronic lithium treatment may occur. Specificity of the assay technique as applied to plasma is discussed. This is the first report of the direct measurement of PGF in a psychiatric disorder.


Nocturnal erections, differential diagnosis of impotence, and diabetes.

In this study it is shown that monitoring of nocturnal penile tumescence (NPT) is an objective method for determining the erectile status of patients who complain of impotence. The characteristics of 11 diabetic patients with abnormal NPT, 11 patients with normal NPT and no medical disorders, and 11 normal men are presented. Also described are several sociodemographic characteristics of the first 100 patients undergoing an NPT evaluation as part of a screen for patients seeking implantation of a penile prosthesis. It is suggested that NPT monitoring should be a component of the differential diagnosis procedure for every patient who complains of impotence and that it provides a tool for the concentrated study of the mechanisms of erection and impotence.


Influence of the antiparkinsonian drugs on the plasma level of neuroleptics.

The interaction between various neuroleptics and antiparkinsonian drugs was analyzed by measuring the neuroleptic plasma level before and after withdrawal of antiparkinsonian drugs. The population completing the study consisted of 32 chronic schizophrenics treated with chlorpromazine (8), levomepromazine (14), thioridazine (6), or haloperidol (4). Twenty-five were also receiving benztropine; 4, trihexyphenidyl; and 3, procyclidine. During the first 4 weeks patients remained on neuroleptics and antiparkinsonians, the latter being withdrawn during the 5th week, and the neuroleptics alone being administered during 16 following weeks. The plasma level of neuroleptics was assayed by gas liquid chromatography, once weekly in the morning at two different times. The analysis of variance showed a significant difference in neuroleptic plasma level when patients took neuroleptics only versus the period they had received neuroleptics and antiparkinsonians. The multiple comparison based on Studentized range Q0-05 revealed a significant progressive increase of neuroleptic plasma level during 12 weeks after withdrawal of antiparkinsonian drugs after which a plateau was reached. The hypothetical mechanisms of action of antiparkinsonians on neuroleptic plasma level are discussed.


Behavioral characteristics of three children with the broad thumb-hallux (Rubinstein-Taybi) syndrome.

Behavioral characteristics of three children with Broad Thumb-Hallux or Rubinstein-Taybi (R-T) syndrome were compared with those of a somewhat comparable clinic sample (N - 15) of children with organic syndromes and retardation. A number of mutual, behavioral resemblances of the three R-T children to each other were found to be absent or less prominent in the comparison group; these included: (i) the R-T children were more emotional and excitable; (ii) more often had nightmares and engaged in self-stimulation; (iii) had greater difficulty getting over anger (pouted); (iv) were friendly and more readily accepted social contacts; (v) had short attention span; and (vi) experienced more difficulty in planning motor acts, and in executing locomotor and oculomotor skills. The pattern of R-T mutual resemblances and their differences from other clinic children logically suggest what may be the behavioral characteristics of children with the R-T syndrome. Educational and child-management suggestions are provided based on the observed and tested characteristics which are presumably related to the R-T syndrome.


Interrelation between plasma magnesium and 25 hydroxy-vitamin D3 levels in chronic renal failure.

In a series of 18 patients suffering from varying degrees of chronic renal failure treated by diet alone, there was a statistically significant positive correlation between plasma magnesium levels and plasms 25 hydroxycholecalciferol (25 HCC) levels. This is thought to be due either to the direct action of 25 HCC on the bone liberating magnesium from bone crystal, or to an increased intestinal absorption of magnesium caused by 25 HCC.


Negative effect of frusemide pretreatment in glycerol induced acute renal failure.

It is commonly assumed that the decrease in the effective circulatory volume (ECV) is the major event in acute renal failure (ARF) and the preferential ischemia of the cortex another major modification. Frusemide has been given to try to prevent this change in glycerol-induced ARF because of its effect in redistributing renal blood flow from medulla to cortex. Isontonic saline was also tried to avoid the ECV depletion. The pretreatment with frusemide not only fails to protect against the ARF but increases its severity. Isotonic saline adminstration and replacement of urinary losses almost prevent glycerol-induced ARF but when both isotonic  saline frusemide are administered together their effect is only a slight increase in the excretion rate of urea and creatinine during the first days of the experiment. The importance of the changes in the ECV or a possible direct action of frusemide on the renin-angiotensin axis are discussed. There is a good correlation between plasma creatinine levels and interstitial oedema. The importance of the oedema in the maintenance of ARF is discussed.


The determination of dissolved nitrogen in blood by gas phase chromatography.

A method for measuring dissolved nitrogen in blood is described. Gas-phase chromatography is used. The apparatus  is provided with a column of 5 A molecular sieve material and with an extraction chamber. CO2 and O2 are absorbed. As in Lenfant's method, extraction  by equilibration is completed by elution. The main features are: the design of the extraction chamber, faciliting gas flow; an auxiliary circuit for freeing the chamber and the reagents from nitrogen, in which the pressure can be equilibrated against the inlet pressure of the column; the care taken to avoid any kind of contamination; the use of a special guide mounted on the blood-transfer syringe, which makes it possible to get reproducible samples at last the checking and measurement of the residual nitrogen which makes it possible to extract and measure the whole of the dissolved nitrogen. At the present stage, the accuracy of the method is better than 1.5% and the coefficient of variation of the reproducibility is 0.57%. These results make the method suitable for measuring (PaN2-PAN2) in cases of chronic respiratory insufficiency.


Bronchial lympho-epithelial nodules in the rat: definition and morphological characteristics in optical and electron microscopy.

Three type of structures can be distinguished among the bronchial lymphoid tissue: lymph nodes, lymphoids cells aggregates and lymphoepithelial nodules. Such structures are encountered in many species and may be characterized by flattened epithelium, devoid of mucus producing cells, infiltrated with lymphocytes and containing of few ciliated cells. The lymphoepithelium surrounds the nodules, characterized by a high cellular density. Original structures may be observed, mainly inter and intracellular vacuoles. Peripheral lymphatic vessels and high endothelium veins contribute to the important lymphocyte transfer. Electron microscope, studies support the view that lymphoepithelium has an uptake function of particulate matter; more direct evidence is however attempted. An hypothesis of capacity for antigenic recognition of the lymphoepithelium nodules is discussed.


Discrepancies in nude mice.

With the increasing number of publications in which nude mice are used, there is a growing list of apparent discrepencies. To avoid such problems, we propose the use of nude mouse populations with a large gene pool which will leave, if possible, the nude allele as the only homozygote. All phenotypic characters consistently different between nu/nu, nu/+ and +/+ mice could then, with more certainty, be linked with the nude mutation.


Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis.

The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid-citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine-exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable.


X-linked syndrome of platelet dysfunction, thrombocytopenia, and imbalanced globin chain synthesis with hemolysis.

An unusual family is described with a congenital bleeding disorder present in four males belonging to three generations. Of the three surviving affected males, all had splenomegaly and petechiae. The three had moderate thrombocytopenia (55-90 X 10(9)/liter) and markedly prolonged Ivy-template bleeding times (greater than 30 min). They were also noted to have reticulocytosis and, upon further investigation, imbalanced globin chain synthesis resembling that of beta-thalassemia minor. Studies on nine additional family members in four generations were normal except for slight elevations of reticulocyte counts in female members, one of whom had the abnormal globin chain synthesis ratio. In male members, the bleeding tendency and clinical signs always occurred in the presence of the globin chain synthesis defect and reticulocytosis. This previously undescribed condition was apparently transmitted as an X-linked disorder.


Autooxidation as a basis for altered function by polymorphonuclear leukocytes.

To investigate the possibility that human polymorphonuclear leukocytes (PMN) elaborate sufficient amounts of hydrogen peroxide (H2O2) and other radicals of reduced oxygen to be autotoxic and retard directed cell movement and phagocytosis, the rate of ingestion of opsonized lipopolysaccharide-paraffin oil particles and movement through Nuclepore filters were studied. Ingestion rates were increased under anaerobic conditions and in normal aerobic conditions in the presence of extracellular catalase but not superoxide dismutase (SOD) or scavengers of singlet oxygen or hydroxyl radicals. Conversely, ingestion rates were decreased when cells were exposed to H2O2 or a superoxide anion (O2-)-H2O2 generating system of xanthine-xanthine oxidase. Catalase, but not SOD, prevented the effect and also enhanced the directed movement of PMN in normal aerobic conditions. PMN from volunteers administered 1600 U/day of the membrane lipid antioxidant alpha-tocopherol were hyperphagocytic but killed Staphylococcus aureus 502A less effectively than controls, suggesting that less H2O2 was available to damage PMN or kill bacteria. H2O2-dependent stimulation of the hexose monophosphate shunt, H2O2 release from phaogytizing PMN, and fluoresceinated concanavalin A cap formation promoted by H2O2 damage to microtubules were all diminished, but the release of O2- from phagocytizing PMN was not diminished in the vitamin E group. These results support the hypothesis that directed movement and phagocytosis by PMN are attenuated by autooxidative damage to the cell membrane by endogenously derived H2O2 and that the administration in vivo of vitamin E may prevent this damage by scavenging H2O2.


Arterial pressure development in neonatal and young spontaneously hypertensive rats.

Systemic arterial pressure of spontaneously hypertensive rats (SHR) were not detectably different from control rats prior to 3 weeks of age. Arterial pressure was elevated in SHR at 4 weeks compared to Wistar-Kyoto rats. Thus, the term 'prehypertensive stage' should probably be reserved for animals less than 1 month of age when this model is examined.


Laser-induced thrombus formation and vascular reactivity in the microcirculation of the spontaneously hypertensive rat.

Thrombi formation resulting from laser-induced injury to mesenteric circulation has been studied in spontaneously hypertensive (SH) and normotensive rats. The thrombotic reaction was enhanced in both venules and arterioles of the SH rats. In the arterioles of the hypertensive rats, the vasoconstriction which develops downstream from the thrombus is greatly intensified and the time to form microvascular haemostatic plugs significantly decreased in the arterioles of these animals. These phenomena have been explained on the basis of an increased reactivity of the vascular smooth muscle of the SH rats to vasoconstrictor substances liberated from platelets at the site of injury.


Mechanism of potassium relaxation of arterial muscle.

Strips of arterial muscle were prepared from rat tail and femoral arteries and dog mesenteric arteries. All muscles developed a contracture slowly when exposed to a potassium-free solution, but relaxed rapidly when potassium was added to the bath to give a concentration as low as 0.1 mM. The slow contracture is caused by norepinephrine release from intrinsic nerve endings, but the rapid relaxation occurs while the norepinephrine concentration is still high. Contractions produced by exogenous norepinephrine or serotonin in a potassium-free bath were also made to relax by the addition of potassium. After several minutes these relaxations reversed abruptly and spontaneously to return to their original level of contraction. The rapid relaxation was found to be due to an electrogenic transport mechanism which caused hyperpolarization within several seconds after the addition of potassium. This hyperpolarization is believed to be caused by electrogenic ion transport since it exceeded the expected membrane potential based on the potential calculated from potassium concentrations, EK. Hyperpolarization declined within 5-15 min, allowing contraction to redevelop. Ouabain was found to prevent both the potassium-induced relaxation and the cessation of norepinephrine release. However, ouabain prevented relaxation as effectively in denervated as in innervated smooth muscle. We conclude that the initial relaxation of arterial smooth muscle that occurs when potassium is reintroduced into a potassium-free solution is caused by membrane hyperpolarization resulting from the enhanced activity of an electrogenic pump; it is not caused by cessation of norepinephrine release.