Gastrointestinal Replacement Solution

The mean sodium concentration of 61 gastrointestinal aspirations in peritonitis was 103 mEq/l. (S.D. 16·66), of 16 aspirations in vagotomy 88 mEq/l. (S.D. 19·49), of 12 aspirations in perforated duodenal ulcer 81 mEq/l. (S.D. 19·49), and of 15 aspirations in intestinal obstruction 89 mEq/l. (S.D. 19·49). The mean potassium concentrations were 9, 9·9, 13, and 8·8 mEq/l. respectively, and the mean chloride concentrations 122, 131, 125, and 112 mEq/l. respectively. It is suggested that a gastrointestinal replacement solution should contain 100 mEq of sodium, 12 mEq of potassium, and 122 mEq of chloride per litre; 50 g. of dextrose or 100 g. of fructose may be added to provide energy.     

Metabolic acidosis and infant feeding.

Most cows'' milk based formulae for infant feeding present a greater acid load to the infant than breast milk. To determine the effect of this difference the acid base state of 180 healthy term infants was measured on the sixth day of life and related to the type of feed. Those infants fed on cows'' milk formula (SMA) had a mean pH of 7-34 +/- 0-05 and a base deficit of 8-8 +/- 3-1, while those fed on breast milk had a mean pH of 7-38 +/- 0-05 and a base deficit of 5-6 +/- 3-1. The difference between the two groups of infants was significant for both these measurements. Metabolic acidosis was defined as a base deficit greater than 10 mmol/l. Seventy-four per cent of the 34 infants who were acidotic at six days were bottle-fed. There was a significant correlation between the pH of the feed and the degree of acidosis in the infant as measured by the base deficit. The findings suggest that when breast milk is not available a pH-adjusted milk formula would be desirable for preventing and treating neonatal metabolic acidosis.     

Treatment of Diabetic Coma with Continuous Low-dose Infusion of Insulin

Thirty-eight patients in diabetic coma from four different centres were treated with a continuous low-dose intravenous infusion of insulin at an average dose of 7·2 IU/hr. All patients recovered rapidly except for one profoundly shocked patient who died. The mean fall in plasma glucose was 58% four hours after the start of insulin. Blood ketone bodies and plasma free fatty acids showed a similar response. There was no significant difference in plasma glucose response according to severity of acidosis or previous treatment with insulin. Hypokalaemia was uncommon. In the treatment of diabetic coma this technique has proved simple, safe, and effective.     

Lacticacidosis: A Clinically Significant Aspect of Shock

A study was made of the metabolic acidosis of hypotensive shock in 25 patients in an attempt to elucidate its etiology and to determine if the degree of acidosis might be a good parameter for the evaluation of treatment and prognosis.Blood lactate was elevated (> 1.3 mEq./l.) in 24 of 25 patients in hypotensive shock. There was a good correlation (r= 0.83, p < 0.01) between rising blood lactate and decrease in serum bicarbonate and arterial pH, early in shock. These data indicate that the metabolic acidosis of early shock is largely due to lactate ion. Evidence is presented that high blood lactate levels early in shock are indicative of poor prognosis.     

The Clinical Significance of Elevated Blood Lactate

Three patients with elevated blood lactate values are described. The first, despite moderate hyperlactatemia of 5.3 mEq./1. and severe acidosis with an arterial blood pH of 6.98, had no “excess lactate”. In a second patient, moderate acidosis with a pH of 7.27 and blood lactate of 7.5 mEq./1., of which 33% was excess lactate, was found to be secondary to tissue hypoxia on an ischemic basis and preceded the onset of clinical shock by four hours. A third patient, diabetic and under treatment with phenformin hydrochloride, presented with many features suggestive of pulmonary embolism, including marked pulmonary hypertension. A diagnosis of idiopathic lactic acidosis was established when the arterial blood pH was found to be 6.77 and a blood lactate value of 14.2 mEq./1., 60% as excess lactate, was discovered in the absence of a demonstrable cause of tissue hypoxia. Exploration of the pulmonary vascular bed showed no sign of mechanical blockage. The diagnostic, therapeutic and prognostic value of measuring blood lactic acid, and of quantitating the proportion circulating as “excess lactate”, is emphasized.     

Hypothermia: a complication of diabetic ketoacidosis.

During 1969-77, 20 episodes of severe hypothermia occurred in 19 diabetic patients in Nottingham. Thirteen were associated with ketotic hyperosmolar coma, two with lactic acidosis, and one with hypoglycaemia, while in four there was no loss of diabetic control. Ketoacidosis accounted for 11.8% of all admissions for severe accidental hypothermia and was a commoner cause than hypothyroidism (8%). Patients with ketoacidosis were younger and developed hypothermia as often during the summer as during the winter. The metabolic disturbance was characteristic, with severe acidosis (mean pH 7.04), a high blood glucose concentration (mean 56.6 mmol/l; 1020 mg/100 ml), and high plasma osmolality (mean 379.7 mmol (mosmol)/kg). Eight of the 13 episodes proved fatal. Hypothermia may aggravate ketoacidosis and complicate treatment and should be sought in all patients with severe diabetic coma.     

Post-partum Hypercalcaemia in Treated Hypoparathyroidism

Two patients with post-thyroidectomy hypoparathyroidism were observed throughout three pregnancies. Their normal maintenance treatment with vitamin D remained unaltered. Serum calcium levels remained normal until shortly before delivery but rose rapidly in the immediate postpartum period to peak levels of 7·8, 6·0, and 6·8 mEq/l. while still on normal or reduced maintenance treatment. This apparent increased sensitivity to vitamin D after delivery persisted for as long as three months.     

The Effect on Serum Ionic Magnesium of Exchange Transfusion with Citrated as Opposed to Heparinized Blood

Serum Mg++ levels before, during, and after replacement transfusion were determined in 20 newborn infants. In 10 infants exchanged with acid-citrate-dextrose (ACD) blood, the level fell from 1.75 ± 0.16 mEq./l. to 0.99 ± 0.16 mEq./l. By contrast, levels in 10 infants exchanged with two types of heparinized blood were unchanged: the pre-exchange values were 1.59 ± 0.11, and the postexchange levels were 1.59 ± 0.08 mEq./l. Mean values for donor bloods were 0.42 ± 0.07 mEq./l. with ACD blood, and 1.45 ± 0.03 mEq./l. with heparinized blood. In vitro studies involving the addition of known amounts of citrate to standard Mg++ solutions demonstrated that the citrate caused a reduction of ionic magnesium. It is proposed that the fall in serum Mg++ when ACD blood is used for exchange transfusion is the combined result of Mg++ binding by the citrate, and the dilution effect of the relatively large proportion of anticoagulant to blood (1:3) used with the ACD mixture.     

Impaired renal functional reserve and albuminuria in essential hypertension

The stimulatory effects of an infusion of amino acids on glomerular filtration rate has previously been used to measure renal functional reserve and detect glomerular hyperfiltration. Thirty four patients with mild to moderate essential hypertension and seemingly normal renal function and 22 healthy controls were given infusions of amino acids to investigate whether renal functional reserve is reduced in essential hypertension and to detect patients at risk of renal damage. Although basal creatinine clearance increased after the infusion of amino acids in the controls (mean 27·9 ml/min; 95% confidence interval 18·2 to 37·6), the overall change was lower in the patients (mean 13·4 ml/min; 8·3 to 18·5), 11 of the 34 showing no increase at all. In these 11 non-responders the mean systolic blood pressure was higher than that in the 23 others (178·5 mm Hg v 157 mm Hg, respectively). Mean urinary albumin excretion was abnormal in the patients (93·3 mg/24 h; 44·2 to 142·4); eight of the 11 non-responders had an albumin excretion above the normal range (>20 mg/24 h). In the 11 patients without renal functional reserve a positive correlation was found between basal creatinine clearance and albumin excretion (r=0·695).As consumed renal reserve and albuminuria are markers of glomerular hyperfiltration studying renal function before and after infusion of amino acids can detect hypertensive patients at risk of progressive renal damage.     

A Low Serum Bicarbonate Concentration as a Risk Factor for Mortality in Peritoneal Dialysis Patients

Background and Aim

Metabolic acidosis is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, this relationship has not yet been determined in peritoneal dialysis (PD) patients.

Methods

This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum bicarbonate (TA-Bic) levels, we aimed to investigate whether a low serum bicarbonate concentration can predict mortality in these patients.

Results

Among the baseline parameters, serum bicarbonate level was positively associated with hemoglobin level and residual glomerular filtration rate (GFR), while it was negatively associated with albumin, C-reactive protein (CRP) levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. After adjustment for age, diabetes, coronary artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea, nPCR, and percentage of lean body mass, TA-Bic level was associated with a significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI, 0.76-0.91; p < 0.001). In addition, compared to patients with a TA-Bic level of 24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a 13.10- and 2.13-fold increased risk of death, respectively.

Conclusions

This study showed that a low serum bicarbonate concentration is an independent risk factor for mortality in PD patients. This relationship between low bicarbonate levels and adverse outcome could be related to enhanced inflammation and a more rapid loss of RRF associated with metabolic acidosis. Large randomized clinical trials to correct acidosis are warranted to confirm our findings.     

Impaired Relaxation in Aorta from Streptozotocin-diabetic Rats: Effect of Aminoguanidine (AMNG) Treatment

Aim The effect of 8 weeks′ streptozotocin (STZ)- induced diabetes and aminoguanidine (AMNG), the inhibitor of advanced glycosylation reaction, treatment on arteriolar reactivity to vasoactive substances was investigated in vitro. Materials and Methods Studies were performed in untreated control rats (n = 10), STZ-induced (60 mg/kg i.v.) diabetic rats (n = 10), AMNG-treated (600 mg/l given in drinking water throughout 8 weeks) control rats (n = 10) and AMNG-treated (600 mg/l given in drinking water, beginning at 72h after STZ and throughout 8 weeks of diabetes) diabetic rats (n = 10). Results are expressed as the mean ±s.e. Relaxant responses are expressed as a percentage (%) relaxation of noradrenaline-induced tone. Statistical comparisons were made by one-way analysis of variance (ANOVA) followed by Tukey–Kramer multiple comparisons test. Results 1. The decreased body weights (205 ± 6 g) and increased blood glucose levels (583 ± 8 mg/dl) of diabetic rats were partially restored by treatment of aminoguanidine (253 ± 6 g, p < 0.05 and 480 ± 14 mg/dl, p < 0.001, respectively). 2. Diabetes caused a 71% deficit in maximal endothelium-dependent relaxation to acetylcholine for noradrenaline precontracted aortas (p < 0.001). AMNG treatment prevented the diabetes-induced impairment in endothelium dependent relaxation (58 ± 8%) to acetylcholine, maximum relaxation remaining in the non-diabetic range (78 ± 4%). 3. Neither diabetes nor treatment affected endothelium-independent relaxation (pD₂ and max. Relax.) to sodium nitroprusside. 4. Vasoconstrictor responses (pD₂ and Max. Contraction) to noradrenaline and KCl were not influenced by the diabetic state and treatment. Conclusion Our data suggest that 8 weeks of experimental diabetes is associated with a decreased endothelium-dependent vasodilatation. AMNG treatment may prevent diabetes-induced endothelial dysfunction. This may be mediated via the prevention of advanced glycosylation end product formation, the enhanced release of vasodilator substances such as prostacyclin, the increased elasticity of blood vessels, the antioxidant activity and inhibitor activity of enzyme aldose-reductase by AMNG.     

Acid-base Balance in Acute Gastrointestinal Bleeding

Acid-base balance has been studied in 21 patients with acute upper gastrointestinal bleeding. A low plasma bicarbonate concentration was found in nine patients, accompanied in each case by a base deficit of more than 3 mEq/litre, indicating a metabolic acidosis. Three patients had a low blood pH. Hyperlactataemia appeared to be a major cause of the acidosis. This was not accompanied by a raised blood pyruvate concentration. The hyperlactataemia could not be accounted for on the basis of hyperventilation, intravenous infusion of dextrose, or arterial hypoxaemia. Before blood transfusion it was most pronounced in patients who were clinically shocked, suggesting that it may have resulted from poor tissue perfusion and anaerobic glycolysis. Blood transfusion resulted in a rise in lactate concentration in seven patients who were not clinically shocked, and failed to reverse a severe uncompensated acidosis in a patient who was clinically shocked. These effects of blood transfusion are probably due to the fact that red blood cells in stored bank blood, with added acid-citrate-dextrose solution, metabolize the dextrose anaerobically to lactic acid. Monitoring of acid-base balance is recommended in patients with acute gastrointestinal bleeding who are clinically shocked. A metabolic acidosis can then be corrected with intravenous sodium bicarbonate.     

The structure of an acylated inositol mannoside in the lipids of propionic acid bacteria

1. Lipids were extracted from five strains of Propionibacterium with chloroform–methanol mixtures and fractionated by chromatography on silicic acid. 2. All five extracts contained a glycolipid composed of fatty acids, inositol and mannose in the molar proportions 2:1:1. 3. Hydrolysis of the glycolipid with alkali gave a mixture of fatty acids and O-α-d-mannopyranosyl-(1→2)-myoinositol. 4. Analysis of the fatty acids by g.l.c. showed that they were predominantly straight- and branched-chain isomers of pentadecanoic acid and heptadecanoic acid. 5. The location and distribution of the fatty acid residues in the molecule was established by periodate oxidation studies and mass spectrometry. The structure of the major glycolipid is 1-O-pentadecanoyl-2-O-(6-O-heptadecanoyl-α-d-mannopyranosyl)myoinositol. 6. The glycolipids are located in the membrane; the cell walls are devoid of lipid. 7. Possible functions of the glycolipid are discussed.     

Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy

Six men aged 26-35 years with proteinuria due to insulindependent juvenile-onset diabetes were treated for moderate hypertension (mean blood pressure 162/103 mm Hg) and studied for a mean of 73 months for the effect on the progression of nephropathy. All patients were of normal weight. During a mean control period of 28 months before treatment the mean glomerular filtration rate (three or four measurements) was 86·1 ml/min and mean 24-hour urinary albumin excretion (also three or four measurements) 3·9 g (range 0·5-8·8 g).During antihypertensive treatment the mean systolic blood pressure fell to 144 mm Hg and mean diastolic pressure to 95 mm Hg. In the control period five patients had shown a mean monthly decline in glomerular filtration rate of 1·23 ml/min; with antihypertensive treatment, however, this decline fell to 0·49 ml/min (2p=0·042). In the remaining patient the glomerular filtration rate was 137 ml/min before treatment and 135 ml/min at the end of the treatment period. In all patients the mean yearly increase in albumin clearance (expressed as a percentage of the glomerular filtration rate) fell from 107% before treatment to 5% during treatment (2p=0·0099).This small study indicates that antihypertensive treatment slows the decline in renal function in diabetic nephropathy. Clinical trials beginning treatment in the incipient phase of diabetic nephropathy will define the optimal modality of treatment in this large patient population.     

Nutritional Studies on Xanthan Production by Xanthomonas campestris NRRL B1459

The nutritional requirements of Xanthomonas campestris NRRL B1459 for optimal xanthan production were studied in a chemically defined medium. Of the carbon sources tested, a 4% sucrose or glucose medium yielded the highest xanthan titers. The further addition of certain organic acids, such as succinate, pyruvate, and α-ketoglutarate, stimulated xanthan production; excess concentrations of these organic acids inhibited xanthan formation. Certain amino acids (e.g., glutamate) and nitrate salts were superior to ammonium salts for xanthan production. Concentrations of these nitrogen sources higher than the optimal levels inhibited xanthan production while stimulating growth. Xanthan production was also sensitive to high concentrations of inorganic phosphate. High xanthan potencies, up to 30 g/kg of broth, were achieved in these shake-flask studies, in which completely defined media were used.     

Small-intestinal Cell Turnover in Patients with Parasitic Infections

Small-intestinal deoxyribonucleic acid (DNA) loss rates were measured in six patients with Strongyloides stercoralis hyperinfestation, in four patients with hookworm disease, and in eight normal controls. In the four patients with strongyloidiasis having weight loss, hypoproteinaemia, and oedema the mean DNA loss rates were 73·9, 51·6, 58·0, and 62·2 ng atoms DNA-P/min respectively, which was significantly higher than that of patients with hookworm disease (mean 17·3, S.D. 6·6) or in eight control subjects (mean 14·5, S.D. 7·5). In two of three patients with strongyloidiasis the high DNA loss rates fell to normal after treatment, and in two others investigated only after treatment the rates were normal. It is suggested that the high epithelial cell turnover in these patients may result in excessive loss of endogenous substances and that this may be an important mechanism in causing malnutrition and hypoproteinaemia in patients with S. stercoralis hyperinfestation.     

Osmotic and ionic regulation during hypoxia in the medicinal leech, Hirudo medicinalis L.

The concentrations of inorganic and organic ions and osmolality in the blood of the medicinal leech, Hirudo medicinalis, were determined during normoxia and hypercapnic and hypocapnic hypoxia. In normoxic animals, the blood sodium concentration was 124.5 +/- 4.2 mmol/l and the total cation concentration was 132.2 +/- 4.3 mEq/l (mean +/- S.D.). Major anionic compounds were chloride (40.8 +/- 1.6 mmol/l), bicarbonate (8.4 +/- 1.3 mmol/l), and organic anions (42.5 +/- 2.3 mEq/l). Among the latter, malate accounts for 30.4 +/- 2.2 mEq/l. The nature of the remaining anion fraction, which balances cation and anion concentrations in leech blood, remains unknown. Within 96 h of hypercapnic hypoxia, the amount of organic osmolytes in leech tissue increased from the control level of 56.6 +/- 9.1 to 158.3 +/- 19.5 mumol/g dry weight. An even higher amount of organic acids was accumulated within 96 h of hypocapnic hypoxia (218.0 +/- 53.7 mumol/g dry weight). A possible reason for this is that lactate, which is a major end-product of hypocapnic hypoxia, cannot be excreted to the external medium as easily as propionate. The accumulation of blood organic acids generating osmotic stress in the animals was compensated by an equimolar decrease in sodium and chloride ion concentrations. In hypercapnic animals these changes resulted in a constant osmotic concentration of the blood (200 mosmol/kg H2O) during the experimental period. Between 24 and 96 h of hypocapnic hypoxia, however, the increase in the osmotic gradient between animal and medium was correlated with further net water uptake and the obvious deterioration of the volume- and ion-regulatory mechanisms in these animals.     

Acute Pancreatitis and Diabetic Ketoacidosis in Accidental Hypothermia and Hypothermic Myxoedema

Serial serum amylase and blood glucose levels were measured in 68 hypothermic (rectal temperature 35°C or less) patients, including 15 who had hypothermic myxoedema (serum protein bound iodine 3·5 μg/100 ml or less). Raised amylase levels were found in 34 patients and probably reflected a mild acute pancreatitis. The high amylase levels correlated with low arterial PO₂ levels and significantly with high arterial PCO₂ levels and the base deficit but not with the severity or duration of the hypothermia. The acute pancreatitis does not explain why hypothermic patients with myxoedema have a poorer prognosis than those who are euthyroid. The pancreatitis occasionally contributed to the development, sometimes delayed, of diabetic ketoacidosis, blood glucose levels of over 120 mg/100 ml being found in 20 patients. There was a significant correlation between the raised serum amylase levels and the hyperglycaemia. Hypoglycaemia, sometimes profound, was found in 12 patients.     

Task-specific performance fatigability and the bilateral deficit during isokinetic leg extensions

Objectives:The purpose of the present study was to compare the fatigue-induced changes in performance fatigability, bilateral deficit, and patterns of responses for the electromyographic (EMG) and mechanomyographic (MMG) amplitude (AMP) and mean power frequency (MPF), during unilateral and bilateral maximal, fatiguing leg extensions.Methods:Nine men (Mean±SD; age =21.9±2.4 yrs; height =181.8±11.9 cm; body mass =85.8±6.2 kg) volunteered to perform 50 consecutive maximal, bilateral (BL), unilateral dominant (DL), and unilateral non-dominant (NL) isokinetic leg extensions at 180°·s^-1, on 3 separate days. Electromyographic and MMG signals from both vastus lateralis (VL) muscles were recorded. Repeated measures ANOVAs were utilized to examine mean differences in normalized force, EMG AMP, EMG MPF, MMG AMP, MMG MPF and the bilateral deficit.Results:The results demonstrated a Condition × Repetition interaction for normalized force (p=0.004, η²_p=0.222) and EMG MPF (p=0.034, η²_p=0.214) and main effects for Repetition for EMG AMP (p=0.019, η²_p=0.231), MMG AMP (p<0.001, η²_p=0.8550), MMG MPF (p=0.009, η²_p=0.252), and the bilateral deficit (p<0.001, η²_p=0.366).Conclusions:The findings demonstrated less performance fatigability during the BL than the unilateral tasks, likely due to a reduced relative intensity via interhemispheric inhibition that attenuated the development of excitation-contraction coupling failure during the BL task.     

Management of metformin-associated lactic acidosis by continuous renal replacement therapy

Background

Metformin-associated lactic acidosis (MALA) is a severe metabolic failure with high related mortality. Although its use is controversial, intermittent hemodialysis is reported to be the most frequently used treatment in conjunction with nonspecific supportive measures. Our aim was to report the evolution and outcome of cases managed by continuous renal replacement therapy (CRRT).

Methodology and Principal Findings

Over a 3-year period, we retrospectively identified patients admitted to the intensive care unit for severe lactic acidosis caused by metformin. We included patients in our study who were treated with CRRT because of shock. We describe their clinical and biological features at admission and during renal support, as well as their evolution. We enrolled six patients with severe lactic acidosis; the mean pH and mean lactate was 6.92±0.20 and 14.4±5.1 mmol/l, respectively. Patients had high illness severity scores, including the Simplified Acute Physiology Score II (SAPS II) (average score 63±12 points). Early CRRT comprised either venovenous hemofiltration (n = 3) or hemodiafiltration (n = 3) with a mean effluent flow rate of 34±6 ml/kg/h. Metabolic acidosis control and metformin elimination was rapid and there was no rebound. Outcome was favorable in all cases.

Conclusions and Significance

Standard use of CRRT efficiently treated MALA in association with symptomatic organ supportive therapies.