Do heart failure patients understand their diagnosis or want to know their prognosis? Heart failure from a patient's perspective.

The management of heart failure has evolved to become a multidisciplinary affair. Constraints of time and resources limit the amount of counselling that is given to heart failure patients in hospital and, with the advent of community heart failure specialist nurses, there is a trend to move more of these services into the community. Most heart failure patients are elderly and may find the information given to them, at the time of diagnosis and later on at home by heart failure nurses, difficult to grasp. In this study, patients' perspectives of a diagnosis of heart failure, their understanding of the diagnosis as well as what being diagnosed with heart failure means to them were recorded. Patients were questioned on whether the news of the heart failure diagnosis was broken to them in a sympathetic manner and how they felt about the information provided at diagnosis.

Closure of loop ileostomies: is early discharge safe and achievable?

A prospective audit of the complications associated with reversal of a loop ileostomy was carried out between March 2000 and March 2005. The complication rate, length of inpatient hospitalisation and re-admission rate were assessed in 100 patients, in a single clinical practice. The median (interquartile range) length of time between the primary procedure and closure was 133 days (120-270) days. Median length of inpatient stay was two days (one - three) days. The overall complication rate was 18%. One patient had a post-operative leak leading to local abscess formation. This was drained surgically after initial failure with radiological drainage. A second patient had a late leak, three weeks after closure, leading to fistula formation. This patient required surgical resection of the anastomosis after failure of conservative management. Twelve patients were re-admitted with small bowel obstruction (12%), of whom 11 were managed conservatively, while one underwent further surgery. There was one post- operative death as a result of acute cardiac failure secondary to undiagnosed hypertensive cardiomyopathy. Thus early discharge following closure of a loop ileostomy, can be achieved with an acceptably low serious complication rate.

Detection of cell-affecting agents with a silicon biosensor.

Cellular metabolism is affected by many factors in a cell's environment. Given a sufficiently sensitive method for measuring cellular metabolic rates, it should be possible to detect a wide variety of chemical and physical stimuli. A biosensor has been constructed in which living cells are confined to a flow chamber in which a potentiometric sensor continually measures the rate of production of acidic metabolites. Exploratory studies demonstrate several applications of the device in basic science and technology.

Testing ocular irritancy in vitro with the silicon microphysiometer.

The silicon microphysiometer, an instrument based on the light-addressable potentiometric sensor, was evaluated as an in vitro alternative for assessing ocular irritancy potential. It indirectly and non-invasively measures cell metabolism by determining the rate of acid metabolite production from cells, in this case human epidermal keratinocytes, placed inside the microphysiometer chamber. The 17 materials used for the evaluation included bar soaps, a liquid hand soap, shampoos, dishwashing liquids, laundry detergents, a fabric softener and several single chemicals. All materials tested were in liquid form. The in vivo irritancy potential of the materials was obtained from historical data using the rabbit low-volume eye test. There was a positive correlation between the in vivo irritancy potential of the test materials and the concentration of test material that decreased the acidification rate of cells by 50% (MRD(50); r = 0.86, P < 0.0001). Preliminary studies suggest other endpoints obtainable from the system may also provide useful information for making ocular safety assessments. Because the method is non-invasive, it is possible to determine whether cells recover from a treatment with the test material. The metabolic rate of the cells also increases at sub-inhibitory concentrations of some of the test materials. Because of the good correlation between the in vivo and in vitro data, the ease with which test materials can be applied to the system, and the multiple endpoints available from the system, it holds great potential as a useful in vitro alternative for ocular safety testing.

Different strains of rats develop different clinical forms of adjuvant disease.

Evidence is presented that a single injection of bacterial antigen in oil into a footpad of rats of 5 strains induced different clinical forms of adjuvant disease in the individual rat strains. Rats were injected with 300 micrograms heat-killed Mycobacterium tuberculosis in 50 microliters paraffin. Inflammatory lesions and clinical features were recorded on skeletal charts at frequent intervals after injection; methods of charting and quantifying the features are described. By individually marking the rats and using one or more charts per rat we obtained an objective record of the course of disease in each animal and thus a means of distinguishing clinical features from manifestations of disease severity. Evaluation of these records showed that there was a pattern of joint involvement and associated physical and clinical features specific to each strain and that such strain specificity was reproducible in groups of rats injected over periods up to 3 1/2 years. These results suggest that the clinical form of adjuvant disease developing in each rat in response to the injection of mycobacteria in oil is genetically determined, and that there are additional factors that interact with genetic ones to allow adjuvant disease to develop in a particular rat.

Immunological unresponsiveness during induction of experimental autoimmune orchitis in guinea-pigs: studies in vivo and in vitro.

Groups of male and female guinea-pigs were immunized with homologous sperm derived from testis (TS) or epididyimis (ES) in Freund's complete adjuvant (FCA). In vivo investigations included skin tests at 2 weeks and development of aspermatogenesis (testis weight) at 4 weeks; in vitro assays were inhibition of migration of peritoneal exudate cells (PEC) and culture of blood leucocytes (lymphocyte transformation) at weekly intervals after immunization. Antigens used were heat-treated extracts of sperm used for immunization (BTS, BES); cells were also cultured simultaneously with PPD. Skin tests revealed anergy in males as compared with females: a larger quantity of antigen which caused partial unresponsiveness in females, caused profound unresponsiveness in males although the aspermatogenesis was less severe. In vitro tests also showed anergy during the active stages of the orchitis. This was non-specific for PEC (specific unresponsiveness was not excluded), but blood leucocytes showed only specific unresponsiveness (to BES). These and previous studies suggest that the unresponsiveness results from a desensitisation by sperm antigens released during the development of aspermatogenesis.

Morbidity following dental extraction. A comparative survey of local analgesia and general anaesthesia.

A survey of morbidity following dental extraction has been carried out. No great differences were found between the morbidity experienced by those patients who had a general anaesthetic and those who had local analgesia. Comparison with the results of a survey conducted by other workers in 1961 shows that modern anaesthetic techniques have virtually eliminated cyanosis and that absenteeism following extractions has increased.

Comparison of allergic aspermatogenesis with that induced by vasectomy. I. In vivo studies in the guinea-pig.

Groups of male and female guinea-pigs were immunized with homologous epdidymal sperm in Freund's complete adjuvant (FCA) and skin tested at weekly intervals with a heat-treated extract of the sperm or with PPD. In females, the skin response to both antigens was similar to that to any standard protein antigen. In males, the response to sperm extract varied with the induced auto-immune orchitis, reaching a maximum immediately after testis lesion was most severe and as recovery was beginning (shown histologically): the response to PPD was decreased at 1 week after immunization, but subsequently was similar to that in females. Skin tests on guinea-pigs 8 months after bilateral vasectomy (when both ends of vasa were ligated), showed no evidence of delayed hypersensitivity to sperm, although there was marked histological evidence of reduced spermatognesis, due to back pressure atrophy.

PIP: The skin response in guinea pigs at various times after immunization with epididymal sperm in Freund's complete adjuvant is reported. Findings were correlated with the progression of the autoimmune orchitis. Also, possible skin reactivity to sperm extract at 8 months after bilateral vasectomies in which both ends of the vasa had been ligated was investigated. The histological changes in the testes at 5 months postvasectomy were studied. Epididymal sperm was obtained by flushing out the vas and epididymis of mature guinea pigs. The dried epididymal sperm was used for immunization, dissolved or suspended in PBS. For skin testing, a heat-treated extract of the sperm (BES) was used. The methods of preparing reagents is described. The skin reactions to BES and to a purified protein derivative (PPD) in females were similar to those of any standard protein antigen. In males, this reaction resembled that in females at 1 week after immunization but later was different. Induration and erythema were greater in females (p less than .001) from 2 weeks on. The response of males to PPD was less than in females at 1 week but at 2 weeks was the same. Males immunized with purified ovalbumin responded to PPD similarly to females. After 8 months, following vasectomy, the response to BES at 24 hours was similar to that of controls. Testes weighed at 1 week after immunization were increased, possibly due to edema, but after the 3rd week weight was decreased. Histology of the testes after immunization showed cellular infiltration after 2 weeks and disappearance of spermatogenic elements from the seminiferous tubules. Evidence of delayed hypersensitivity to sperm was not shown.

Comparison of allergic aspermatogenesis with that induced by vasectomy. II. In vitro studies of cell-mediated immunity to sperm after vasectomy in man and guinea-pig.

Transformation of peripheral blood leucocytes was shown to be a valid assay for cell-mediated immunity to sperm in male guinea-pigs immunized with homologous epididymal sperm (ES) in FCA. A heat-treated extract of ES (BES) was used for culture. Possible developement of cell-mediated immunity to sperm after vasectomy was investigated in patients and guinea-pigs, by culture of blood leucocytes before and at intervals after operation. Patients' leucocytes were cultured with a heat-treated extract of human seminal sperm (BHS); guinea-pigs' leucocytes were cultured with BES. These cultures showed no evidence of specific stimulation of leucocytes by sperm extract, up to 1 year after vasectomy in patients, or up to 6 months in guinea-pigs. Similarly, no evidence of delayed hypersensitivity could be demonstrated by skin tests with BES in animals vasectomized 1 year previously. We consider that this study establishes that cell-mediated immunity to sperm does not develop in either man or guinea-pigs, up to 1 year after conventional vasectomy.

PIP: In vitro studies of cell-mediated immunity to sperm after vasectomy in man and guinea-pig are reported. Transformation of peripheral blood leucocytes was shown to be a valid assay for cell-mediated immunity to sperm in male guinea-pigs immunized with homologous epididymal sperm (heat treated extract-BES) in FCA. Patients' leucocytes cultured with a heat-treated extract of human seminal sperm, and guinea-pigs' leucocytes cultured with BES revealed no evidence of specific stimulation by sperm extract up to 1 year and 6 months postvasectomy, respectively. Also, no evidence of delayed hypersensitivity could be seen by skin tests with BES in animals vasectomized 1 year previously. It is concluded that cell-mediated immunity to sperm does not develop in man or guinea pigs up to 1 year postvasectomy.

Inferior vena caval tamponade following partial hepatectomy for liver injury.

A case of acute obstruction of the inferior vena cava after partial hepatectomy for liver injury is described. The underlying haemodynamics and prevention of this complication are discussed.

First-aid for snake-bite: efficacy of a constrictive bandage with limb immobilization in the management of human envenomation.

A herpetologist was bitten on the thumb by a common brown snake (Pseudonaja textilis). A constrictive bandage to impede lymphatic and capillary flow was applied, and the upper limb was immobilized. Two hours after the bite, there were no signs of symptoms of envenomation and venom (to a sensitivity of 0.5 ng/mL) was undetectable in serum and urine. Within five minutes of removal of the constrictive bandage, significant signs of envenomation developed, and serum and urine levels of venom rose significantly. The patient received two ampoules of brown-snake antivenom, and had recovered within six hours. No anaphylaxis of other allergic phenomena occurred, despite the fact that three other doses of antivenom had been administered in the preceding 36 months for prior elapid envenomation. By means of an experimental whole-mouse technique, and an enzyme-linked immunospecific assay (ELISA) system, the snake involved was shown to deliver 4.91 mg of venom in an average bite. A constrictive bandage properly applied to impede lymphatic and capillary flow, together with limb immobilization, is effective in the field management of human elapid envenomation.

Consequences of vasectomy: an immunological and histological study related to subsequent fertility.

Studies of 2 groups of patients 2 years and 8 years following vasectomy failed to demonstrate evidence of cell mediated immunity to sperm. Histological examination of testicular tissue from 11 patients undergoing reversal of vasectomy showed significant abnormalities in each. However, subsequent fertility within 15 months occurred in 7 (63.6%) of these patients. The nature of the testicular changes and the possible aetiological factors are discussed.

PIP: A total of 42 patients was studied in vitro for cell-mediated immunity to sperm using lymphocyte transformation technique. A prior study of 23 patients who had had vasectomy was continued at 4 to 6 monthly intervals to complete a 2nd year following the vasectomy. Another group of 19 patients who had had vasectomy 2 to 8 years before was similarly studied for evidence of cell-mediated immunity to sperm. 11 of these patients subsequently had vasovasostomy with testicular biopsy at time of reversal. Histologically, the testicular tissues of the 11 patients during vasovasostomy exhibited significant abnormalities; all had intertubular edema and reduced spermatogenesis. The histological abnormality was not related to the duration of the vasectomy. 63.6% (7) of the wives of the 11 patients who had vasovasostomy conceived 5 to 24 months (average, 11.3 months) following anastamosis. The rest had euspermia and oligozoospermia. The histological abnormality was not associated with subsequent fertility or conception time. The in vitro study concluded that cell-mediated immunity to sperm did not occur within 1 year of vasectomy in man. The current study suggests that cell-mediated immunity to sperm does not occur at all after vasectomy; evidence for conception within a short time of operation indicates that fertility is not affected by persisting immune response to sperm.

The occurrence of Hb E Saskatoon in Scotland.

The finding of several examples of Hb E Saskatoon in the Orkney Islands, in Edinburgh and in individuals of Scottish descent in Canada but nowhere else, suggests that the original mutation occurred in Scotland, perhaps in the Orkneys.

Continuous monitoring of receptor-mediated changes in the metabolic rates of living cells.

Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular metabolic rates. Changes in cell metabolism were monitored continuously with a previously described silicon-based microphysiometer that detects small changes in extracellular pH. The amplitude and kinetics of the metabolic changes depend upon several factors including pretreatment of the cells prior to receptor stimulation, the dose of hormone/neurotransmitter used, and the receptor complement of the cells. Responses are receptor specific; cells transfected with receptor genes respond only to the appropriate hormone/transmitter, whereas control (nontransfected) cells or cells transfected with different receptors exhibit no response. The specificity of the responses was further documented by using pharmacological antagonists. In Chinese hamster ovary (CHO) cells transfected with human beta 2-adrenergic receptors, isoproterenol produces a 20-60% increase in the rate of extracellular acidification with an EC50 of 4 nM, a response that is competitively antagonized by (-)-propranolol. The EC50 for the isoproterenol response is shifted from 4 nM to 100 nM in the presence of 3 nM (-)-propranolol. The kinetics of the metabolic response induced by beta-adrenergic receptor stimulation are markedly slower than those elicited by muscarinic receptor agonists. The maximal metabolic response in cells transfected with beta-adrenergic receptors peaks at approximately 12 min as compared with less than 30 sec in cells transfected with muscarinic receptors, perhaps reflecting activation of different second-messenger pathways. These findings illustrate an alternative means of studying cellular responses to hormones and neurotransmitters and suggest that metabolic changes will be generally useful for detecting the consequences of receptor-ligand interactions.

GM-CSF triggers a rapid, glucose dependent extracellular acidification by TF-1 cells: evidence for sodium/proton antiporter and PKC mediated activation of acid production.

The extracellular acidification rate of the human bone marrow cell line, TF-1, increases rapidly in response to a bolus of recombinant granulocyte-macrophage colony stimulating factor (GM-CSF). Extracellular acidification rates were measured using a silicon microphysiometer. This instrument contains micro-flow chambers equipped with potentiometric sensors to monitor pH. The cells are immobilized in a fibrin clot sandwiched between two porous polycarbonate membranes. The membranes are part of a disposable plastic "cell capsule" that fits into the microphysiometer flow chamber. The GM-CSF activated acidification burst is dose dependent and can be neutralized by pretreating the cytokine with anti-GM-CSF antibody. The acidification burst can be resolved kinetically into at least two components. A rapid component of the burst is due to activation of the sodium/proton antiporter as evidenced by its elimination in sodium-free medium and in the presence of amiloride. A slower component of the GM-CSF response is a consequence of increased glycolytic metabolism as demonstrated by its dependence on D-glucose as a medium nutrient. Okadaic acid (a phospho-serine/threonine phosphatase inhibitor), phorbol 12-myristate 13-acetate (PMA, a protein kinase C (PKC) activator), and ionomycin (a calcium ionophore) all produce metabolic bursts in TF-1 cells similar to the GM-CSF response. Pretreatment of TF-1 cells with PMA for 18 h resulted in loss of the GM-CSF acidification response. Although this treatment is reported to destroy protein kinase activity, we demonstrate here that it also down-regulates expression of high-affinity GM-CSF receptors on the surface of TF-1 cells. In addition, GM-CSF driven TF-1 cell proliferation was decreased after the 18 h PMA treatment. Short-term treatment with PMA (1-2 h) again resulted in loss of the GM-CSF acidification response, but without a decrease in expression of high-affinity GM-CSF receptors. Evidence for involvement of PKC in GM-CSF signal transduction was obtained using calphostin C, a specific inhibitor of PKC, which inhibited the GM-CSF metabolic burst at a subtoxic concentration. Genistein and herbimycin A, tyrosine kinase inhibitors, both inhibited the GM-CSF response of TF-1 cells, but only at levels high enough to also inhibit stimulation by PMA. These results indicate that GM-CSF activated extracellular acidification of TF-1 cells is caused by increases in sodium/proton antiporter activity and glycolysis, through protein kinase signalling pathways which can be both activated and down-regulated by PMA.