Effect of lignocaine and pH on propofol-induced pain.

Propofol has the disadvantage of pain on injection. A higher partition of propofol in the aqueous phase of the preparation causes a higher incidence of pain on injection while addition of 1% lignocaine to propofol reduces pain. The low concentration of this local anaesthetic and the rapid pain relief observed indicates that mechanisms other than local anaesthesia are involved, that is change in pH. We performed a clinical study to investigate the influence of lignocaine and pH on pain during injection of 1% Diprivan. Ten parts of 1% Diprivan were mixed with one part of saline, 1% lignocaine or hydrochloric acid to achieve the same pH as that after addition of lignocaine. Diprivan 1% mixed with 1% lignocaine and with hydrochloric acid gave mean pain ratings (1-10) of 0.32 (SD 0.75) (n = 25) and 0.88 (1.30) (n = 24), respectively. These ratings were significantly lower than ratings after injection of a saline-Diprivan mixture (2.18 (2.06), n = 22). The pH of the 1% Diprivan formulation decreased after mixing with 1% lignocaine. The concentration of propofol in the aqueous phase was lower when 1% Diprivan was mixed with 1% lignocaine (0.376 g litre-1) or HCl (0.392 g litre-1) compared with 1% Diprivan and saline (0.476 g litre-1) mixed in the same proportion. Thus pH changes may modify propofol-induced pain on injection by a mechanism different from the effect of the local anaesthetic on the vascular endothelium. Our findings may explain why lignocaine mixed with propofol causes less pain than injection of lignocaine followed by propofol.

Umbilical cord blood sampling--a tool for delivery quality control?

BACKGROUND: Regular cord blood analysis post partum is regarded by many as one of the most accurate and objective methods of auditing intrapartum care. Emergency cesarean sections and ventouse deliveries, due to the threat of asphyxia, are examples where post partum acid base data from the umbilical artery ought to be a must. The possibility of having cord blood analyses as a routine at all deliveries was investigated in this study. METHODS: During a two month period blood samples were drawn from both the umbilical artery and vein at all vaginal deliveries and cesarean sections between 8 am and 4 pm. Samples were analysed for a complete acid base status and lactate concentration. RESULTS: True paired artery-venous samples for acid base data and lactate concentrations were obtained from 48% of the women. Sampling was especially difficult after emergency cesarean section and vaginal twin deliveries. Lactate analyses gave the same information about the metabolic state of the newborn as did BEecf. CONCLUSIONS: Cord blood acid base data are a superior method of retrospective analyses of CTG-tracings and partographs within a quality control program relating to intra partum care. However, routines for cord blood sampling must be well established in both the delivery room and in the operating theater to obtain samples from the umbilical artery in cases of threatening intrapartum asphyxia. A graph for easy post partum documentation and interpretation of acid base data is introduced.

The counterregulatory response to hypoglycaemia in women with the polycystic ovary syndrome.

OBJECTIVE: The pathogenetic mechanisms behind insulin resistance in polycystic ovary syndrome (PCOS) are far from fully elucidated. Aberrant counterregulatory responses to hypoglycaemia have been reported in patients with insulin resistance, and recent reports suggest that plasma glucose may be regulated at lower levels in women with PCOS. In this study we investigated the complete hormonal counterregulatory response to hypoglycaemia in women with PCOS. DESIGN: Prospective cross-sectional study. PATIENTS: Eight obese (BMI > or = 25) and 10 non-obese (BMI < 25) women with PCOS, diagnosed by means of ultrasonography and clinical signs of chronic anovulation. Eight obese and 9 non-obese controls. MEASUREMENTS: Hypoglycaemia was induced by an intravenous bolus of soluble insulin (0.15 IU/kg body weight). The counterregulatory responses of cortisol, GH, catecholamines, glucagon, chromogranin A (CGA), and neuropeptide Y (NPY) were studied together with symptoms of hypoglycaemia. RESULTS: The obese women with PCOS had a more pronounced truncal-abdominal body fat distribution (waist hip ratio, WHR) and were hyperinsulinaemic, compared with the obese controls. All the women exhibited blood glucose levels (< 2 mmol/l) well below the threshold for the hormonal counterregulatory response and for the appearance of clinical symptoms. The non-obese women with PCOS showed a greater increase in serum concentrations of GH than the lean controls. The obese women with PCOS exhibited blunted responses of noradrenaline and NPY, but similar increases of adrenaline and CGA, compared with the obese controls. They also showed a lower symptom score during hypoglycaemia. The response of noradrenaline to hypoglycaemia correlated inversely with fasting insulin levels in the women with PCOS. Among all the obese women (PCOS and controls pooled) basal levels of noradrenaline correlated inversely with the WHR. CONCLUSIONS: All the women with PCOS, independent of BMI, body fat distribution and insulin levels, showed preserved counterregulatory responses to hypoglycaemia. The reduced plasma levels of noradrenaline and the lower perception of hypoglycaemic symptoms in the obese women with PCOS could both reflect a lower activation of the sympathetic nervous system. This aberration seems related to truncal-abdominal obesity and hyperinsulinaemia. The finding of an increased response of GH in the lean women with PCOS could support previous suggestions of an altered activity of the GH/IGF-I system in these women.

Combination of gadolinium and dysprosium chelates as a cellular integrity marker in MR imaging.

A combination of gadolinium (Gd) and dysprosium (Dy) chelates was investigated as a potential marker of cell-membrane integrity by means of a double-contrast effect in MR imaging. Blood samples with varying hematocrit (Hct) levels containing intact or lysed cells were used as model systems. With intact cells, the agents were assumed to be distributed solely extracellularly and the highest Hct studied (69%) was assumed to mimic the ratio of extracellular to intracellular water in tissue. The combined effect on image intensity of Gd (in a concentration corresponding to 0.2 mmol/kg b.w. in humans) and Dy (0.6 mmol/kg b.w.) applied simultaneously was a marked difference in signal intensity between samples with intact and lysed cells in both the T1- and T2-weighted spin-echo images with a corresponding increase in the contrast-to-noise ratio. This was the result of a T1 reduction caused by Gd with a negligible Dy susceptibility effect in areas with lysed cells. On the other hand, the Dy susceptibility effect (i.e. reduced apparent T2) dominated in areas with intact cells. Thus, the combination of Gd and Dy may serve as a marker of cell-membrane integrity in MR examinations.

Hypoxanthine, xanthine, and urate in synovial fluid from patients with inflammatory arthritides.

As nucleotide catabolism increases during tissue injury the appearance of purine metabolites in inflamed synovial fluid might be of value in understanding the joint damage in inflammatory arthritides. In this study, therefore, synovial and plasma concentrations of hypoxanthine, xanthine, and urate in 16 patients with rheumatoid arthritis (three with psoriatic arthropathy) were analysed. It was found that their plasma concentrations of hypoxanthine were greater than those of a reference group of healthy subjects. The synovial fluid concentrations of hypoxanthine, xanthine, and urate were higher than corresponding concentrations in plasma. Positive correlations were found between the respective plasma and synovial fluid values of xanthine and urate. These findings indicate a local enhanced purine metabolism in inflamed joint tissue and diffusion of oxypurines from joint cavity to plasma. No relation was found between measured metabolites and disease duration, radiological joint findings, or synovial fluid cells. Except for a weak correlation between plasma urate and serum haptoglobin, measured purine metabolites were not related to laboratory measures of systemic inflammation.

Splanchnic oxygen consumption in septic and hemorrhagic shock.

Oxygen consumption (VO2) is dependent on oxygen delivery (DO2) in septic shock. Local hypoxia with later secondary organ failure may develop, however, despite an often hyperdynamic circulation. The splanchnic organs seem to be of vital importance in this context. In experiments performed in pigs we compared total body VO2 and DO2 with oxygen consumption and delivery in the gastrointestinal organs and the liver in two different shock states: (1) septic shock induced by peritonitis (n = 6) and (2) hemorrhagic shock (n = 6). Another group of six animals not in shock served as controls. Total, gastrointestinal, and liver DO2 decreased in a similar pattern in both septic and hemorrhagic shock. Gastrointestinal and liver VO2 increased in sepsis, whereas it was unchanged in hemorrhage. In the later phase of sepsis, liver VO2, but not gastrointestinal VO2, again decreased, because liver oxygen extraction was almost total and liver DO2 decreased further. The development of flow-dependent liver hypoxia was reflected in a decrease in liver lactate turnover (increased liver lactate release) during late sepsis. Early hypoxia in the splanchnic region is suggested as a plausible mechanism behind the development of secondary organ failure, especially in sepsis.

Uridine, xanthine and urate concentrations in prostatic fluid and seminal plasma of patients with prostatitis.

The etiology of prostatitis is not fully understood and several causative factors have been considered in the past. In this study we analyzed the expressed prostatic secretion (EPS) and seminal plasma with regard to uridine, xanthine, urate, creatinine and zinc from patients with prostatitis (the diagnosis was based on symptoms for at least 1 year), together with creatinine, urate and zinc in the serum. In 8 of the patients, a direct comparison of these constituents was performed between EPS and seminal plasma. EPS contained low concentrations of uridine and xanthine and high concentrations of creatinine and zinc as opposed to seminal plasma that displayed a reverse pattern. The mean urate concentration in seminal plasma, exceeding that of EPS by 78%, was rather close to the mean value found in serum but no significant correlation was seen between urate in serum and urate in seminal plasma or EPS. Urate in EPS correlated significantly to xanthine in EPS and such a relationship was also observed between urate and creatinine in EPS. In seminal plasma, urate and xanthine were likewise correlated with each other. On division of the patients into a high-score symptom group and a low-score group, no intergroup differences were found in EPS and seminal plasma constituents. Hence, we found high concentrations especially of uridine and xanthine in seminal plasma, compared with other body fluids, and evidence of a backflow of urine mixing with the prostatic fluid of these patients was seen. We suggest that crystal formation of these metabolites may occur under certain conditions and could constitute a first step in the development of prostatitis-vesiculitis-epididymitis in some cases.

Cerebrospinal fluid calcium, parathyroid hormone, and monoamine and purine metabolites and the blood-brain barrier function in primary hyperparathyroidism.

Psychiatric disturbances are common in primary hyperparathyroidism (HPT), but their pathogenesis is essentially unknown. This study deals with cerebrospinal fluid (CSF) calcium homeostasis and its connection with parathyroid hormone (PTH), blood-brain barrier (BBB) function, and central monoamine and purine metabolites in patients with primary HPT. In 22 patients with primary HPT (serum calcium 2.85 +/- 0.21 mmol/l), the CSF concentrations of total and ionized calcium were higher (1.21 +/- 0.08 mmol/l, p less than 0.01, and 1.09 +/- 0.05 mmol/l, p less than 0.001, respectively) than in 11 normocalcemic reference subjects. The values correlated with serum calcium concentration (p less than 0.001) and CSF/serum albumin ratio, a measure of BBB permeability. The latter ratio was elevated in one-third of the patients with HPT, indicating BBB damage. CSF immunoreactive intact PTH was higher in the HPT patients than in the reference group (p less than 0.05), and serum and CSF PTH were positively correlated (p less than 0.05). The CSF levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were lower, and the level of urate in CSF was higher, in the HPT patients than in the reference subjects, while there were no consistent differences in CSF hypoxanthine or xanthine. CSF 5HIAA correlated inversely with CSF ionized calcium (r = -0.42, p = 0.02). After parathyroid surgery, CSF calcium and urate decreased significantly and CSF monoamine metabolites increased slightly. The decrease in CSF ionized calcium correlated with the alleviation of psychiatric symptoms. The results indicate the importance of increased CSF calcium concentrations in patients with primary HPT and suggest a relation between central calcium regulation and central turnover of monoamines.

Serological studies of an SLE-associated antigen-antibody system discovered as a precipitation reaction in agarose gel: the HAKATA antigen-antibody system.

Current population studies indicate that the HAKATA antigen is one of the normal plasma proteins not yet completely characterized. The frequency of Japanese donor, patients and Swedish patients was 100%, 99.99% and 99.98%, respectively. Anti-HAKATA antibody production was found in three patients, all with systemic lupus erythematosus (SLE). Transient HAKATA antigen deficiency was found in 13 patients and appeared to be strongly associated with SLE (11 out of 13). None of the 14 SLE patients had a history of transfusion. It is therefore concluded that anti-HAKATA antibody is produced as one of the autoantibodies in SLE.

Lack of success with a combination of alanine and phosphoenolpyruvate as an additive for liquid storage of red cells at 4 degrees C.

Red cells were stored at 4 degrees C in a storage solution containing alanine or alanine plus phosphoenolpyruvate (PEP). The intention was to investigate whether alanine and PEP might act synergistically to maintain a normal level of both red cell ATP and 2.3 diphosphoglycerate (2.3 DPG) under normal liquid storage conditions. Storage in the presence of alanine kept the red cell concentration of 2.3 DPG higher than the reference solution for an extended period of time, provided the initial pH was about 7.0 (37 degrees C). When the pH of the storage solution containing alanine plus PEP was lowered to facilitate the transport of PEP into the red cells, the concentration of 2.3 DPG was lowered to a rate equal to that in the reference solution. The level of ATP was also about the same as in the reference solution. The majority of the added PEP was continuously converted to 2 phosphoglycerate and 3 phosphoglycerate in the extracellular fluid. A small amount of unconverted PEP penetrated the red cell membrane when the pH went below 6.5; this occurred after 3 weeks of storage. The intracellularly located PEP, however, was not metabolized to 2.3 DPG to any significant extent within the first 6 weeks of storage. These findings indicate that PEP is not suitable as an additive for liquid storage of red cells at 4 degrees C. The combination of alanine and PEP that theoretically could be a suitable additive for liquid storage of red cells was not satisfactory in practice.

Continuous recording of muscle nerve sympathetic activity during percutaneous transluminal angioplasty in renovascular hypertension in man.

We have previously shown that during percutaneous transluminal renal angioplasty (PTRA) there is a transient increase in plasma renin activity (PRA) that is partly mediated by adrenergic beta-receptors. Despite a concomitant increase in plasma aldosterone, no increase in blood pressure occurred. The aim of this study was to record sympathetic outflow in man during PTRA as reflected by muscle nerve sympathetic activity and arterial plasma noradrenaline. Nine patients with hypertension and unilateral renal artery stenosis underwent PTRA by the Grüntzig technique and simultaneous microelectrode recording of muscle nerve sympathetic activity in the peroneal nerve. Blood pressure and heart rate were recorded and blood specimens were drawn for determination of noradrenaline and PRA. During total occlusion of the renal artery, muscle nerve sympathetic activity and the heart rate were unchanged. In the first 6 min after occlusion PRA increased transiently, but there was no significant change in muscle nerve sympathetic activity, arterial noradrenaline, heart rate or blood pressure. From 10 min after PTRA, muscle nerve sympathetic activity was significantly increased and after 40 min there was a significant increase in noradrenaline. The heart rate remained unchanged throughout the procedure, but the blood pressure decreased progressively and the diastolic blood pressure was significantly reduced at 40 min, indicating successful dilation. Despite activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, two strong pressor systems, the only circulatory reaction was a decrease in diastolic blood pressure. These findings indicate simultaneous activation of a potent depressor mechanism during PTRA.

Sympathetic response to oral carbohydrate administration. Evidence from microelectrode nerve recordings.

Microneurography was used to measure sympathetic outflow in human muscle nerves (MSA) for up to 90 min after the ingestion of 100 g D-glucose, 75.8 g D-xylose, intravenous D-glucose (0.35 g/kg), and 300 ml water. 19 healthy subjects were examined using a microelectrode positioned in the right peroneal nerve. MSA increased from 21 +/- 0.9 bursts/min at rest to 36.9 +/- 4.3 bursts/min 30 min after ingestion of D-glucose and from 18.9 +/- 2.9 to 26.3 +/- 3.4 bursts/min 30 min after D-xylose. The increase in MSA was already significant by 15 min. MSA had not returned to the basal level after 90 min. Neither intravenous D-glucose nor water intake enhanced MSA. MSA increased in parallel with plasma norepinephrine, and a significant correlation (r = 0.55; P less than 0.001) was observed between the plasma insulin concentration and MSA after D-glucose ingestion. In three subjects the outflow of sympathetic nerve activity to the skin was examined after oral D-glucose and no change was observed, emphasizing the differentiated nature of the sympathetic nerve response to carbohydrate. Multiple factors such as insulin alone, hemodynamic adjustment to splanchnic vasodilation, and gastrointestinal distension are probably involved in the increased muscle nerve sympathetic outflow after carbohydrate ingestion.

Plasma volume substitution does not inhibit plasma noradrenaline and muscle nerve sympathetic responses to insulin-induced hypoglycaemia in healthy humans.

Microelectrode recordings of muscle nerve sympathetic activity and measurements of venous plasma noradrenaline have indicated increased sympathetic outflow during acute hypoglycaemia. Plasma volume reduction during hypoglycaemia, as evidenced by increasing peripheral venous haematocrit might underly the sympathetic activation. To study the effect of prevention of plasma volume reduction during hypoglycaemia, saline containing albumin was infused intravenously in healthy adult volunteers during hypoglycaemia. Hypoglycaemia was induced by an intravenous injection of soluble insulin in a dose of 0.15 IU/kg body weight. Peripheral venous plasma noradrenaline concentrations were identical in experiments without and with plasma volume substitution. Muscle nerve sympathetic activity increased to the same extent during hypoglycaemia with and without plasma volume substitution. It is concluded that increased plasma noradrenaline concentrations and enhanced muscle nerve sympathetic activity during insulin-induced hypoglycaemia in man are not consequences of plasma volume reduction.

Phosphoenolpyruvate in the rejuvenation of stored red cells in SAGM medium: optimal conditions and the indirect effect of methemoglobin formation.

Red cells stored in saline-adenine-glucose-mannitol (SAGM) medium were rejuvenated by incubation with phosphoenolpyruvate (PEP) under conditions that can be achieved easily in ordinary blood banking. Regeneration of 2,3 diphosphoglycerate (2,3 DPG) and adenine nucleotides of stored red cells was dependent on the pH of the incubation medium and the incubation time. In red cells stored for 3 and 5 weeks, the optimal pH and incubation time for regeneration of 2,3 DPG and adenine nucleotides were 5.8 and 90 minutes and 6.1 and 60 minutes, respectively. During the incubation of red cells with PEP, methemoglobin was formed; it increased when the medium pH was below 6.0 and the incubation time exceeded 60 minutes. We conclude that incubation at a medium pH of 6.1 for 60 minutes is optimal for the rejuvenation of stored red cells with PEP. Under such incubation conditions, the concentrations of 2,3 DPG and adenine nucleotides in red cells stored for 5 weeks were restored to normal without methemoglobin formation.

Amino acid concentrations in cerebrospinal fluid in presenile and senile dementia of Alzheimer type and multi-infarct dementia.

Free amino acid levels were measured in cerebrospinal fluid (CSF) from demented patients (D, n = 30) suffering from presenile and senile dementia of Alzheimer type (PDAT, n = 7; SDAT, n = 9), multi-infarct dementia (MID, n = 14) and a reference sample group consisting of young neurotic patients (R, n = 16). Comparing the amino acid levels in the dementia subgroups, significantly higher alanine, methionine, phenylalanine and tyrosine levels were found both in MID and SDAT vs. PDAT. No difference was seen between SDAT and MID. Compared to the reference sample group, higher glycine levels were found in each dementia subgroup; higher alanine, methionine and ornithine levels in MID, and SDAT; and higher phenylalanine levels in MID. In PDAT the level of tyrosine was lower. Coefficients of correlation were calculated between amino acid levels and age, and the findings in the reference sample groups were divergent from those observed in dementia. The differences observed are discussed in terms of amino acid, carbohydrate and neurotransmitter metabolism.

The relation between urinary tract infections and stone composition in renal stone formers.

During a seven-year period (1975-1981) a total of 1325 patients hospitalized for stone disease were studied as to the occurrence of positive urine cultures. Urinary stones from 535 surgically treated patients were analyzed with infrared spectrophotometry and the relationships between stone composition, level of surgery and bacteriological strains were studied. Positive urinary cultures were found in 34% of the surgically treated patients and in 21% of those not operated upon. Among the surgically treated patients with urinary tract infection (UTI) E. coli was the most frequent microorganism (35%), followed by Proteus (28%). Patients with Proteus infection had the highest frequency of UTI episodes, most of which occurred before hospitalization. There was a higher frequency of magnesium ammonium phosphate (MAP) calculi among patients with Proteus infection than among those with non-Proteus infection, in whom no difference in stone composition was found. Patients infected with E. coli had more phosphate-containing stones (CaP+MAP) than non-infected patients. The highest frequency of oxalate calculi (CaOx+CaOx/CaP) was found among patients without infection. No E. coli infections were seen in male patients with CaP and MAP calculi. MAP stones were most often found in the kidney and oxalate stones in the ureter.

Purine metabolites in the CSF in presenile and senile dementia of Alzheimer type, and in multi infarct dementia.

Concentrations of hypoxanthine, xanthine, uric acid and creatinine were measured in CSF of patients suffering form presenile and senile dementia of Alzheimer type (PDAT, SDAT) and multi infarct dementia (MID) and in a reference group of young neurotic patients. There was no difference in hypoxanthine concentration, but there was a marked elevation of xanthine concentration in each dementia group, independent of the type of dementia. There was a significant elevation of uric acid in SDAT and MID but not in PDAT. The concentration of uric acid was higher in MID than in SDAT. There was a higher level of creatinine in the dementia groups, but no difference was seen among the dementia groups. These results are discussed in order to better interpret the etiology and the differentiated diagnosis of the types of dementia.