Septicaemia in the Neutropenic Patient

A total of 29 cases of septicaemia proved by blood culture in 22 severely neutropenic patients with acute leukaemia or aplastic anaemia have been studied. The recovery rate was 75% in the Gram-positive septicaemias and 60% in the Gram-negative septicaemias in which treatment response could be evaluated. Neutropenia predisposed to septicaemia and its degree seemed to be important. The underlying state of the bone marrow was an important prognostic factor; the neutrophil count at the time of diagnosis and the infecting organism were less important. Gentamicin was the single most useful antibiotic, and the infection was controlled largely with gentamicin and one other antibiotic, most often carbenicillin. Possibly a similar result could have been obtained with gentamicin alone, but since the bacterial flora in a given environment is changeable empirical antibiotic regimens should remain flexible.     

Plasma 11-Hydroxycorticosteroid and Growth Hormone Levels in Acute Medical Illnesses

Adrenal cortical response in acute medical illness has been studied by measuring the plasma 11-hydroxycorticosteroid (11-OHCS) concentration in 178 patients. Those with unbalanced diabetes, acute infections, and severe myocardial infarction had high levels. The results obtained suggest that in a patient with a severe infection and hypotension a plasma 11-OHCS level of less than 15 μg./100 ml. indicates an inadequate adrenal cortical response, and one patient with septicaemia and temporary adrenal cortical insufficiency is described. Growth hormone levels were increased in patients with severe diabetic ketosis but not in those with hyperosmolar non-ketotic diabetic coma.     

Effects of Treatment on the Mortality Rate in Septicaemia

The results of treatment have been analysed in 173 patients with septicaemia during 1962–8. Between 1962 and 1965 various antibiotics were used, and shock was treated with vasopressor agents. Between 1966 and 1968 kanamycin was given initially, and shock was treated with corticosteroids and with intravenous fluid therapy monitored with a central venous pressure manometer.The mortality rate in 1966–8 fell to half that of the earlier period in patients with Gram-negative infections, and in those with shock. The reduced mortality in the latter was clearly associated with the use of a central venous manometer to control intravenous fluid therapy, though whether the reduction resulted from specific improvement in intravenous therapy or from the necessary closer observation of the patient is not clear. Staphylococcal septicaemia was common during both periods, and its mortality rate did not fall; hence methicillin together with kanamycin is now given initially in all cases.     

Experience in Monitoring Gentamicin Therapy during Treatment of Serious Gram-Negative Sepsis

This paper reports our experience in monitoring gentamicin therapy during the treatment of 68 episodes of serious Gram-negative sepsis in 65 hospital patients. Most of the patients had major underlying disease. Of those who were adequately treated (peak serum concentrations of 5 μg/ml or more in 72 hours for septicaemia, urinary tract infection, and wound infection; and 8 μg/ml or more at some time during the course of treatment for pneumonia) 84% (46 out of 55) were cured. These serum concentrations could be achieved only by starting with a regimen of 5 mg/kg/day in three divided doses in all adult patients, subsequent dosage being determined by the results of rapid serum assay. The incidence of nephrotoxicity and symptomatic ototoxicity was no greater than in previous series. The main reason for assaying serum gentamicin is to ensure that an adequate dosage is achieved as soon as possible. In patients with impaired renal function or receiving prolonged high dosage assays also serve to guard against an excessive accumulation of gentamicin and an increased risk of toxicity.     

Infectious Complications in Bone Marrow Transplant Patients

In 11 patients receiving transplants of allogeneic bone marrow, the graft was successful in six. Nine patients developed infections, and six died—five of septicaemia and one of Pneumocystis carinii pneumonia. Fifty individual infections occurred. Predisposing factors included severe underlying diseases, long-term exposure to resistant hospital organisms, heavy immunosuppressive therapy, and graft-versus-host disease. Gram-negative bacilli and Candida albicans were the most common causative organisms. In every instance of septicaemia identical organisms were isolated from blood cultures and simultaneously obtained stool cultures. Infection with exogenous organisms often occurred in patients occupying conventional isolation rooms. Isolation of one patient for 45 days in a laminar air flow room prevented infection with exogenous organisms.     

Susceptibility of Neisseria gonorrhoeae to seven antibiotics in vitro

One hundred consecutive isolates of N. gonorrhoeae were tested for susceptibility to penicillin, ampicillin, tetracycline, erythromycin, kanamycin, cephaloridine and cephalexin by an agar dilution method. Relative resistance to penicillin was frequent. For 39% of isolates the minimum inhibitory concentration (MIC) of penicillin was 0.05 U./ml. or less; in 55% the MIC was 0.5 to 2.0 U./ml. Ampicillin was slightly more active than penicillin G: all isolates were inhibited by 0.5μg./ml. or less. Resistance to tetracycline and erythromycin was frequent with MIC of 1 μg./ml. or greater observed in 32 and 24% of isolates respectively. The MIC of kanamycin for all gonococci was 8 μg./ml. or greater. Cephalexin was slightly more active than cephaloridine, though each drug exhibited a wide range of MIC values. Gonococcus isolates resistant to penicillin (MIC of 1.0 U./ml. or greater) tended to be resistant to the other antibiotics tested.     

Treatment of Infections with Colistimethate Sodium (Coly-Mycin)

Colistimethate sodium (Coly-Mycin) was used in the treatment of 17 patients: 13 had urinary tract infections (two of these had positive blood cultures), three had respiratory tract infections, and one patient had both urinary and respiratory tract infections. In nine of the 17 a foreign body—either a carcinoma, a catheter, or a stone—complicated the infection.The dosage used was 1.1-2.3 mg./lb./day with a maximum in one case of 2.4 g. given over an eight-day period. The organisms so treated included Pseudomonas, six; Aerobacter, six and E. coli, two. Both Pseudomonas and Aerobacter were encountered in three cases.On bacteriological grounds, six patients were cured, eight relapsed, and in three the infecting agent was replaced by another organism. The best responses were obtained in those patients with Pseudomonas infection. Side effects included nausea, vomiting, vertigo, paresthesias, and pain at the site of injection.Colistimethate sodium has a place in the treatment of Gram-negative infections excluding Proteus organisms.     

Movements of radioactive sodium in cerebral-cortex slices in response to electrical stimulation

1. Sodium exchange was measured with ²⁴Na in incubated guinea-pig cerebral-cortex slices maintained under adequate metabolic conditions with a steady content of fluid and ions resembling that of brain in vivo. 2. Evidence was obtained indicating that Na⁺ ions behaved in the inulin space as if they were extracellular, and that their entry into the non-inulin space of unstimulated tissue was about 10 times slower and could be separated, on the basis of complete exchangeability, into two components, a `fast' one, which reacted to electrical stimulation, and a `slow' one, exchanging at a rate of about 8μequiv./g./hr., which was not affected by stimulation. 3. The average rate of sodium turnover in unstimulated slices was 175–275μequiv./g./hr., whereas that for stimulated slices was approx. 4–6 times this, or 1050–1180μequiv./g./hr. The stimulated rate was equivalent to a turnover of 32% of the sodium in the non-inulin space/min., or 3mμequiv./g./impulse. 4. Response to the onset of stimulation appeared to be immediate, but after cessation of stimulation increased sodium movements persisted for several minutes before return to unstimulated values. 5. Calculations based on electrochemical gradients suggested that about one-quarter of the energy available from respiration was required for sodium and potassium transport at maximal rates in both unstimulated and stimulated cerebral-cortex slices.     

Plasma Levels of Immunoreactive Corticotrophin in Patients with Cushing's Syndrome

Plasma levels of immunoreactive corticotrophin (A.C.T.H.) have been determined in 56 patients with Cushing''s syndrome by means of a homologous radioimmunoassay. In untreated Cushing''s disease (bilateral adrenal hyperplasia due to excessive A.C.T.H. secretion from the pituitary) plasma values ranged from 40 to 200 μμg./ml., between 8 and 10 a.m., compared with a range in normal subjects of 12 to 60 μμg./ml. Considerably raised levels, often above 2,000 μμg./ml., were found in patients with Cushing''s disease after bilateral adrenalectomy. A.C.T.H. concentrations were usually higher in patients with bilateral adrenal hyperplasia associated with ectopic A.C.T.H. production than in patients with untreated Cushing''s disease; whereas plasma A.C.T.H. was undetectable in the presence of an adrenocortical tumour. All patients with Cushing''s syndrome failed to show the normal circadian rhythm of circulating A.C.T.H. levels.     

Hypophosphataemia and Hyperphosphataemia in a Hospital Population

One hundred cases of hypophosphataemia (≤ 2·0 mg/100 ml) and 84 cases of hyperphosphataemia (≥ 5·0 mg/100 ml) occurring in a hospital population were studied in order to determine the cause of the abnormality. Examples of hyperphosphataemia due to renal failure were excluded from the study.A low serum phosphorus concentration was most frequently due to intravenous administration of carbohydrate, usually glucose, which accounted for 40% of cases. The next commonest cause was vomiting (12%). No obvious explanation could be found in 26% of cases, but in most of these factors were present which are known to affect phosphorus metabolism.No one cause of hyperphosphataemia was outstanding in frequency and in over 50% of cases no definite explanation for the abnormality could be found.     

Intestinal Absorption of Tritium-Labelled Folic Acid in Idiopathic Steatorrhea: Effect of a Gluten-Free Diet

The intestinal absorption of folic acid in patients with idiopathic steatorrhea was studied by the oral administration of tritium-labelled folic acid in a dosage of 15 μg./kg. Results were expressed as a percentage of the orally administered folic acid radioactivity excreted in the urine over 24 hours. The mean excretion of radioactivity in 38 normal subjects was 48.2 ± 16.6% (mean ± SD), whereas eight patients with untreated idiopathic steatorrhea excreted only 16.7 ± 3.4% (mean ± SE).The ability of the gluten-free diet to correct this absorptive defect was demonstrated by the finding of normal values in 11 patients in complete clinical remission for periods exceeding six months after institution of the diet. Serial studies in individual patients indicated that a significant improvement was obtainable in as short a period as two weeks following exclusion of gluten from the diet.     

Glucose metabolism in the superovulated rat ovary in vitro. Effects of luteinizing hormone and the role of glucose metabolism in steroidogenesis

1. Superovulated rat ovary slices from rats treated with 20μg. of luteininzing hormone/100g. body wt. 2hr. before death and from control animals have been incubated in vitro. Output of Δ⁴-3-oxo steroids (0·2μmole/g. wet wt./hr. in control tissue) was linear for 4hr., and was increased by approx. 70% in slices from luteinizing hormone-treated rats. Rate of oxygen consumption (90·0±4·6μmoles/g. wet wt./hr.) was linear for 3hr. and unaltered by luteinizing hormone treatment or addition of glucose (1mg./ml.) to the medium. 2. In slices from control animals, steady-state rate of glucose uptake was 78·0±2·9μg. atoms of carbon/g. wet wt./hr.; steady-state rates of lactate output, pyruvate output and incorporation of [U-¹⁴C]-glucose carbon atoms into carbon dioxide and total lipid extract were 60·7±0·9, 2·4±0·1, 18·0±1·1 and 0·7±0·1μg. atom of carbon/g. wet wt./hr. and accounted for 104·5±1·9% of the glucose uptake. In slices from luteinizing hormone-treated rats, glucose uptake and outputs of lactate, pyruvate and [¹⁴C]carbon dioxide were increased by approx. 25%, and 108·4±3·2% of the glucose uptake could be accounted for. 3. The total lipid extract was separated by thin-layer chromatography and saponification. Of the ¹⁴C incorporated into this fraction during incubation with [U-¹⁴C]glucose 97% was found in the fractions containing glyceride glycerol and less than 3% in the fractions containing sterols, steroids or fatty acids. Appreciable quantities of ¹⁴C were incorporated into these lipid fractions from [1-¹⁴C]acetate. 4. From a consideration of the tissue glycogen content, the specific activities of [¹⁴C]lactate and glucose 6-phosphate (C-1) derived from [1-¹⁴C]-, [6-¹⁴C]- and [U-¹⁴C]-glucose, and the ratio of [¹⁴C]carbon dioxide yields from [1-¹⁴C]glucose and [6-¹⁴C]glucose, it was concluded that there was no appreciable glycogenolysis or flow through the pentose phosphate cycle. 5. In ovary slices from both control and luteinizing hormone-treated animals, glucose in vitro raised the incorporation rate of ¹⁴C from [1-¹⁴C]acetate into sterols and steroids. Luteinizing hormone in vivo stimulated the incorporation rate in vitro but only in the presence of glucose. 6. In slices incubated in medium containing [³H]water, [¹⁴C]sorbitol and glucose (1mg./ml.), the total water space (865±7·1μl./g.) and the extracellular water space (581±22μl./g.) were unchanged by luteinizing hormone treatment in vivo but the glucose space was raised from 540±23·6μl./g. to 639±31·3μl./g. 7. Luteinizing hormone treatment was found to lower the tissue concentration of the hexose monophosphates and to increase the total activity of hexokinase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and possibly of phosphofructokinase. 8. The kinetic properties of a partially purified preparation of phosphofructokinase were found to be qualitatively similar to those from other mammalian tissues. 9. The results are discussed with reference to both the role of glucose metabolism in steroidogenesis and the mechanism by which luteinizing hormone increases the rate of glucose uptake.     

Plasma Digoxin Concentrations in Patients with Atrial Fibrillation

Plasma digoxin concentrations were measured by radioimmunoassay in 116 patients with atrial fibrillation on long-term oral treatment with the drug, and in 23 patients with digoxin toxicity. The mean concentrations were 1·4 ng./ml. and 3·1 ng./ml., respectively. Though an overlap occurred between the therapeutic and toxic ranges, toxicity is unlikely to occur below a level of 2 ng./ml. Plasma concentration showed a poor correlation with resting heart rate during atrial fibrillation. In patients with good renal function, however, a significant correlation was found between oral dose and plasma concentration. No evidence was obtained for increased sensitivity to therapeutic concentrations of the drug in elderly subjects, but the doses required to achieve these concentrations tended to be less than in younger patients.     

Resistance of Pseudomonas aeruginosa to gentamicin

The resistance to gentamicin 4 μg./ml. of 250 Pseudomonas aeruginosa isolates was measured by a proportion method. Twenty-eight (11.2%) of the cultures fell into the most resistant group, in whose populations between 10 and 100% of the organisms were resistant. A relatively high percentage of urinary isolates and a comparatively low percentage of isolates from respiratory sources occurred in this group. Three of the 28 were resistant to carbenicillin 150 μg./ml. and 6 of 18 tested were as resistant to gentamicin 8 μg./ml. as they were to 4 μg./ml. The distribution of Ps. aeruginosa isolates between the different grades of resistance did not change significantly during the 10 months in which the survey was performed.     

II. In vitro studies of antibacterial activity

One hundred and forty isolates of beta-hemolytic streptococcus cultured from patients with clinical pharyngitis were studied by disc diffusion for antibiotic sensitivity to lincomycin, erythromycin, cephalexin and penicillin and by agar dilution to cephalexin and penicillin. All isolates were sensitive to ≤ 0.1 μg./ml. penicillin and ≤ 1.56 μg./ml. cephalexin. The disc-diffusion test was reliable in predicting the sensitivities in vitro. One strain of group A betahemolytic streptococcus was resistant to erythromycin by disc diffusion. When compared to Lancefield grouping 18% of strains were incorrectly identified as group A by the bacitracin-disc test. Cephalexin was uniformly effective in vitro in inhibiting beta-hemolytic streptococci and the 30 μg. cephalexin disc was reliable in predicting these sensitivities.     

Microbial pathogens of the coconut pest Oryctes rhinoceros: influence of weather factors on their infectivity and study of their coincidental ecology in Kerala,India

The rhinoceros beetle, Oryctes rhinoceros L., is an economically important pest of the coconut palm. Management of this pest has been accomplished using microbial agents viz., Oryctes virus (OrV) and an entomofungal pathogen Metarhizium anisopliae. Recently an opportunistic bacterial pathogen Pseudomonas alcaligenes has also been noticed to cause septicaemia in the grubs when under stress. To unravel the influence of abiotic weather factors and the interactions amongst these microbial pathogens, a 3 year study was conducted from September 1996 to August 1999 in three of the southern districts of Kerala, India. Of the 6627 grubs and 307 adults collected from various breeding sites of the pest, 5% of the grubs and 22% of the adults had natural virus infection, 3% larvae died of M. anisopliae mycosis and 20% larvae succumbed to bacterial septicaemia. Oryctes virus infection in grubs and adults was negatively correlated to minimum temperature (correlation co-efficient, r = –0.4, and –0.6 respectively, sample size, n = 0). Increase in relative humidity increased the fungal activity (r = 0.8) whereas, maximum temperature had a negative impact (r = –0.7). Occurrence of virus infection in grubs and adults was positively correlated (r = 0.6), supporting the contention of active transmission of the virus pathogen between these two stages. The bacterial septicaemia in the grubs was marginally correlated with virus infection and P. alcaligenes undermined the efficiency of the virus pathogen.     

Serum and Urinary Folate in Liver Disease

During the active phase of viral hepatitis urinary folate loss was found to be 8·0 to 48·3 (mean 31·1) μg./day, compared with a normal urinary folate excretion of 0·1 to 18·0 (mean 9·5) μg./day. In cirrhosis and cardiac failure with congestive hepatomegaly the corresponding values were 25·8 to 55·0 (mean 35·7) μg./day and 2·5 to 61·6 (mean 26·9) μg./day, respectively. Urinary folate loss may be a significant factor in the aetiology of folate deficiency of chronic liver disease, particularly when dietary intake is poor.After prolonged dialysis in Visking casing urinary folate was almost totally dialysable, but an appreciable fraction of serum folate was not, even after 72 hours. The dialysable (free) folate fraction of serum and urine disappeared maximally during the first six hours'' dialysis, and was virtually cleared after 24 hours'' dialysis; clearance curves in normal individuals and in liver disease were comparable. The non-dialysable serum folate fraction was of similar magnitude in all subjects studied, in spite of marked variation in total folate, and probably represented protein-bound folate.     

The Influence of Body Mass Index on Outcomes in Patients Undergoing Cardiac Surgery: Does the Obesity Paradox Really Exist?

Purpose

Obesity influences risk stratification in cardiac surgery in everyday practice. However, some studies have reported better outcomes in patients with a high body mass index (BMI): this is known as the obesity paradox. The aim of this study was to quantify the effect of diverse degrees of high BMI on clinical outcomes after cardiac surgery, and to assess the existence of an obesity paradox in our patients.

Methods

A total of 2,499 consecutive patients requiring all types of cardiac surgery with cardiopulmonary bypass between January 2004 and February 2009 were prospectively studied at our institution. Patients were divided into four groups based on BMI: normal weight (18.5–24.9 kg∙m⁻²; n = 523; 21.4%), overweight (25–29.9kg∙m⁻²; n = 1150; 47%), obese (≥30–≤34.9kg∙m⁻²; n = 624; 25.5%) and morbidly obese (≥35kg∙m⁻²; n = 152; 6.2%). Follow-up was performed in 2,379 patients during the first year.

Results

After adjusting for confounding factors, patients with higher BMI presented worse oxygenation and better nutritional status, reflected by lower PaO₂/FiO₂ at 24h and higher albumin levels 48h after admission respectively. Obese patients showed a higher risk for Perioperative Myocardial Infarction (OR: 1.768; 95% CI: 1.035–3.022; p = 0.037) and septicaemia (OR: 1.489; 95% CI: 1.282–1.997; p = 0.005). In-hospital mortality was 4.8% (n = 118) and 1-year mortality was 10.1% (n = 252). No differences were found regarding in-hospital mortality between BMI groups. The overweight group showed better 1-year survival than normal weight patients (91.2% vs. 87.6%; Log Rank: p = 0.029. HR: 1.496; 95% CI: 1.062–2.108; p = 0.021).

Conclusions

In our population, obesity increases Perioperative Myocardial Infarction and septicaemia after cardiac surgery, but does not influence in-hospital mortality. Although we found better 1-year survival in overweight patients, our results do not support any protective effect of obesity in patients undergoing cardiac surgery.     

Influence of Achlorhydria on Aspirin-induced Occult Gastrointestinal Blood Loss: Studies in Addisonian Pernicious Anaemia

The effect of aspirin (acetylsalicylic acid) ingestion on occult gastrointestinal blood loss has been studied in patients with treated Addisonian pernicious anaemia and proved achlorhydria and in control patients able to secrete hydrochloric acid. A highly significant increase in gastrointestinal blood loss (1·9 ml./day of treatment) occurred with aspirin ingestion in the achlorhydric patients. The control group had a significantly greater increase in blood loss (4·29 ml./day of treatment). Thus aspirin can produce occult gastrointestinal blood loss by a mechanism unrelated to hydrochloric acid. Half of the control patients had losses of similar magnitude to those in the pernicious anaemia group, and the degree of blood loss in individual control patients appeared unrelated to gastric acidity. Differences in gastric mucosal characteristics, in the rate of gastric emptying, or in systemic effects of aspirin may explain the variation between individuals in the degree of occult gastrointestinal blood loss after aspirin.