Short-chain fatty acids in the treatment of radiation proctitis: a randomized, double-blind, placebo-controlled, cross-over pilot trial

PURPOSE: Treatment of chronic radiation proctitis remains unsatisfactory. Short-chain fatty acids are the preferred energy source for the colonic epithelium. We aimed to determine for the first time whether topical butyric acid enemas relieve symptoms and improve the macroscopic and microscopic findings in chronic radiation proctitis. METHODS: A randomized, double-blind, placebo-controlled, cross-over pilot trial compared patients given two weeks of butyric acid enemas (40 mmol) twice per day with those given placebo, with a one-week washout period; 15 patients were randomized and 12 completed both arms of the trial. A total symptom score combined six symptom items per week (rectal pain, episodes of rectal bleeding, amount of blood passed, days with diarrhea, number of stools, and urgency). Symptom, endoscopic, and histologic scores were obtained at the beginning of the study and again at the last week of each treatment arm. RESULTS: Total symptom score at baseline (median, 5.5) improved for those patients receiving active treatment (median, 3.5), but compared with placebo (median, 4.5), the change was not significant. Endoscopic appearances were largely unaltered by active treatment. Histology was abnormal in 82 percent of patients receiving placebo compared with 55 percent of those given butyric acid enemas (P = not significant). CONCLUSION: Butyric acid enemas do not appear to be superior to placebo in the treatment of chronic radiation proctitis.     

Early onset group B streptococcal disease: clinical, roentgenographic, and pathologic features

Thirty-one neonates with early onset of serious group B streptococcal infections were observed in a four-year period. The mortality was 52%. Premature infants with clinical signs of respiratory distress syndrome were at highest risk of death; clinical signs of RDS were typical until apnea, shock, respiratory failure, and worsening of the radiographic pattern unexpectedly intervened. Pathologic material from infants with radiographic evidence either of RDS or of pneumonia showed both typical hyaline membrane disease and pneumonia in most instances. Factors which may be helpful in recognizing premature infants at risk for GBS disease in the much larger group of premature infants with uncomplicated RDS include: history of artificial, premature, or prolonged rupture of membranes; localized pulmonary infiltrates on chest roentgenogram; low absolute neutrophil count; and an unusually rapid progression of RDS.     

Colorectal cancer. Clinical and pathologic features

Despite an improved understanding of the pathogenesis of colorectal cancer and the technical ability to alter its natural history in a large proportion of average and high-risk patients, this cancer remains deadly. There has been no significant change in incidence or survival rates over the past 40 years. This indicates a continued need for earlier detection of polyps and cancers, aggressive surgery for the primary tumor, and improved multimodality treatment for metastatic disease.     

The diagnosis of ventilator-associated pneumonia: a comparison of histologic, microbiologic, and clinical criteria

STUDY OBJECTIVE: To evaluate histologic, microbiological, and clinical criteria in the recognition of ventilator-associated pneumonia (VAP) in patients who died while mechanically ventilated. METHODS: The study group consisted of 39 patients who died after a mean of 14 days of mechanical ventilation. Postmortem fiberoptic bronchoscopy (FOB) and open lung biopsy were performed with collection of specimens initiated <1 h after death. The microbiological specimens included suction catheter aspirate of tracheal secretions, FOB-guided protected specimen brush (PSB) of tracheal secretions, blindly placed PSB in a distal airway, FOB-guided PSB in a distal airway, and FOB-guided BAL fluid (BALF) in a distal airway. Qualitative bacteriologic study was performed on all specimens, and quantitative bacteriologic study was performed on all but the suction catheter aspirate of the trachea. A biopsy specimen of peripheral lung parenchyma from the same region sampled by FOB was sent for quantitative culture and histologic analysis. The BALF was analyzed for cell population and percent of neutrophils containing intracellular organisms. The clinical criteria selected for comparison with histologic and microbiological results included a temperature > or =38.5 degrees C during the 48 h prior to death, a WBC count > or =15,000/mm3 in the 48 h prior to death, presence of a bacterial or fungal pathogen on the last sputum culture, radiographic worsening in the week prior to death, and worsening gas exchange defined as a 15% decrease in the PaO2/fraction of inspired oxygen ratio in the 72 h prior to death. RESULTS: None of the quantitative cultures had a reliable positive predictive value for histologic pneumonia. None of the five clinical criteria tested showed agreement with the presence or absence of histologic pneumonia. There was a significant correlation between qualitative and quantitative microbiological results from the distal airway/FOB-guided PSB, distal airway/BALF, and quantitative culture of the lung parenchyma. Also, suction catheter aspirate of the trachea had a sensitivity of 87% in recognizing the bacterial species simultaneously present in lung parenchyma. None of the patients with histologic pneumonia had <50% neutrophils in the BALF. CONCLUSIONS: Neither the bacterial, density from the four airway quantitative cultures, nor the bacterial density from quantitative culture of lung parenchyma accurately separated the histologic pneumonia and nonpneumonia groups. No clinical criteria or combination of clinical criteria correlated with the presence or absence of histologic pneumonia. A BALF with <50% neutrophils had a 100% negative predictive value for histologic pneumonia. A BALF quantitative culture had a sensitivity of 63%, specificity of 96%, and positive predictive value of 91% in recognizing sterile lung parenchyma. Thus, BALF may have a role in excluding pneumonia/infection in the ventilated patient. Antibiotic choice for the empiric therapy of VAP can be accurately guided by the microbial population recognized through culture of a tracheal suction catheter aspirate.     

Peripheral blood granulocytes and mononuclear cell responses in monkeys with experimental shigellosis

Between January 1992 and November 1992, four consecutive patients (ages 53 to 81 years) underwent early surgical repair of postinfarction ventricular septal ruptures using a new simple operative technique. The principles of the technique are longitudinal incision of the infarcted left anterior ventricular wall, placement of a saccular patch of single equine pericardium that covers the infarcted left ventricular wall, and large buttressed suture closure of the left ventriculotomy. The infarcted septum and infarcted left ventricular wall are completely separated from the left ventricular cavity. In this procedure, the infarcted myocardium is not resected, and left and right ventricular muscles are preserved. This technique is simple and safe for use in the acute phase of myocardial infarction, and it preserves ventricular function after surgery.     

Acute effects of dietary fatty acids on the fatty acids of human milk

1. Effects on 5-HT function of sibutramine and its active metabolites, BTS 54 354 and BTS 54 505, were compared with fluoxetine, (+)-fenfluramine and (+)-amphetamine. 2. In vitro sibutramine weakly inhibited [3H]-5-HT uptake into brain synaptosomes. BTS 54 354, BTS 54 505 and fluoxetine were powerful [3H]-5-HT uptake inhibitors, whereas (+)-fenfluramine and (+)-amphetamine were very much weaker. Conversely, whilst sibutramine, its metabolites and fluoxetine did not release [3H]-5-HT from brain slices at < or = 10(-5)M, (+)-fenfluramine and (+)-amphetamine concentration-dependently increased [3H]-5-HT release. 3. Sibutramine and fluoxetine had no effect on 5-hydroxytryptophan (5-HTP) accumulation in either frontal cortex or hypothalamus at doses < 10 mg kg(-1). In contrast, (+)-amphetamine ( > or = 3 mg kg(-1)) reduced 5-HTP in hypothalamus, whilst (+)-fenfluramine (> or =1 mg kg(-1)) decreased 5-HTP in both regions. 4. Sibutramine (10 mg kg(-1) i.p.) and fluoxetine (10 mg kg(-1) i.p.) produced slow, prolonged increases of extracellular 5-HT in the anterior hypothalamus. In contrast, (+)-fenfluramine (3 mg kg(-1) i.p.) and (+)-amphetamine (4 mg kg(-1) i.p.) induced rapid, short-lasting increases in extracellular 5-HT. 5. Only (+)-fenfluramine (10 mg kg(-1)) altered 5-HT2A receptors in rat frontal cortex when given for 14 days, producing a 61% reduction in receptor number and a 18% decrease in radioligand affinity. 6. These results show that sibutramine powerfully enhances central 5-HT function via its secondary and primary amine metabolites; this effect, like that of fluoxetine, is almost certainly mediated through 5-HT uptake inhibition. By contrast, (+)-fenfluramine enhances 5-HT function predominantly by increasing 5-HT release. (+)-Amphetamine, though weaker than (+)-fenfluramine, also enhances 5-HT function by release.     

Computer simulation of fatty acids

Fatty acids modified by sulfhydric collectors are investigated. Three-dimensional molecular models are constructed for these acids and the main computer parameters of the total steric energy are determined. Based on the computer design, new reagents are suggested and molecular models are constructed and the total steric energy is calculated for them.     

Cis-unsaturated fatty acids and platelet function

The main method to study platelet function in dietary studies has been the platelet aggregation test in vitro. Even though it is well established that dietary cis-unsaturated fatty acids (FAs) modify platelet aggregation some uncertainty still exists how to interpret the in vitro results in the context of a situation in vivo. The other ways to look at platelet activation are measurements of thromboxane metabolites in urine or the concentration of beta-thromboglobulin (betaTG) released from alpha-granules. Dietary fish oil or long-chain n-3 FAs lower the high basal excretion rate of thromboxane, while only a modest effect is noticed at a low basal excretion rate. Results on the effects of other cis-unsaturated FAs on urinary TXB2 metabolites are almost totally lacking. Furthermore, platelet betaTG release in vivo does not seem to be affected by changes in dietary FAs. The regulatory function of dietary FAs in platelets is extremely complex, and clearly more should be understood about the association between dietary FAs and platelet membrane FAs in connection with platelet responses to physiological stimuli and subsequent signal transduction inside the platelets.     

Dietary fatty acids and blood coagulation

Factor VII coagulant activity (VIIc) is a risk factor for coronary heart disease (CHD). Plasma VIIc is positively associated with dietary fat intake, suggesting that fat-rich diets are accompanied by a hypercoagulable state. Reduction in total fat consumption is followed by a decrease in VIIc within 24 h. In adults taking diets rich in long-chain saturated fatty acids, a postprandial increase in VIIc occurs after a fatty meal irrespective of its fat composition. This effect has dose-response characteristics, persists for several hours, and is due to activation of factor VII. There is no acute effect of dietary fat on factor VII antigen (VIIag) concentration, but VIIag is positively related to dietary fat intake. More studies are needed on the effects of dietary fat composition on fasting and postprandial factor VII. Dietary fat appears to influence both the atherosclerotic and thrombogenic components of CHD.     

Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma

Records of 792 patients with differentiated thyroid carcinoma seen at the Lahey Clinic Foundation over a 40-year period were analyzed; 631 patients had a minimum followup period of 15 years. Differentiated types currently constitute nearly 90% of thyroid carcinomas. The clinical presentation has improved substantially through the years, and the results of treatment generally have improved. The per cent of patients with primarily incurable and locally unresectable disease or distant metastases has decreased from 7% before 1950 to 1% currently, and this group resulted in almost one third of the total fatalities and one half of fatalities within the first 5 years after treatment. Clear relationships were demonstrated between older age, men, extraglandular extension, blood vessel invasion, major capsular involvement, multifocal disease, and higher mortality rates. Lymph node metastases were found to exert a protective effect in all categories of disease analyzed, and this effect was directly related to the number of lymph node metastases present such that no deaths occurred in those patients who had more than 10 node metastases. Surgical treatment recommended is subtotal thyroidectomy for patients at high risk of death from disease as defined by combinations of age, sex, and extraglandular extension. Patients at low risk or with small carcinomas can be treated satisfactorily by lobectomy. Lymph node resections should be of a limited type or a modified neck dissection and should be performed only therapeutically. No improvement, as judged by mortality or recurrence rates, could be demonstrated by the use of radio therapy after surgery, and its use should be discouraged. Thyroid hormone administered for suppression of endogenous thyroid-stimulating hormone production improved mortality rates significantly in patients with papillary and mixed forms of carcinoma in all age groups but did not affect survival in patients with follicular carcinoma of the thyroid.20     

Dietary fat, trans fatty acids, and risk of coronary heart disease

Results from human feeding studies and recent large-scale epidemiologic surveys suggest that dietary trans fatty acids enhance the risk of developing coronary heart diseases. Despite a lack of accurate data regarding dietary intake of trans fatty acids, existing epidemiologic data and evidence from experimental feeding studies support the idea that lowering current intakes of trans fatty acids may lower the risk of coronary heart disease.     

Feeding trans fatty acids to rats has no effect on the intestinal uptake of glucose, fatty acids or cholesterol

Trans fatty acids are produced in the manufacture of margarine, and these hydrogenated fatty acids may have a deleterious effect on the reduction in fasting levels of serum cholesterol anticipated from the feeding of cis polyunsaturated fatty acids. We undertook this study in rats to test the effect of feeding trans fatty acids on the intestinal uptake of glucose, fatty acids and cholesterol. Adult female Wistar rats were fed for 2 weeks semisynthetic, isocaloric diets containing no oleic acid (18:1), cis 18:1 or trans 18:1. There was no difference between the three dietary groups in the animals' food consumption or body weight gain. Rats fed trans 18:1 had an approximately 20% decline in the total weight of the ileum as compared with controls fed no 18:1, and therefore there was also a decline in the percentage of the ileal tissue comprised of mucosa. When comparing rats fed trans 18:1 with those fed cis 18:1 or no 18:1, there was no difference in the uptake of varying concentrations of D-glucose when expressed as nmol.100 mg tissue-1.min-1 or nmol.100 mg mucosal-1.min-1 for jejunum or for ileum. Also, there was no difference in the value of the maximal transport rate (Vmax), Michaelis constant (Km), or the contribution of passive uptake of glucose assessed with L-glucose. There was no diet-associated change in the jejunal or ileal uptake of a medium-chain length fatty acid (lauric acid), a long-chain length saturated fatty acid (palmitic acid), a monounsaturated fatty acid (oleic acid), two polyunsaturated fatty acids (linoleic and linolenic acids), or cholesterol. Thus, we conclude that 2 weeks' feeding of trans fatty acid to rats has no influence on the jejunal or ileal uptake of glucose, fatty acids or cholesterol.     

Red cell membrane fatty acids, cytosolic phospholipase-A2 and schizophrenia

Forty subjects with schizophrenia and 40 age- and sex-matched controls were recruited, and blood samples were obtained for analysis of red cell membrane fatty acid composition by capillary gas chromatography. A blood sample was also taken from the same population to test for allelic association between schizophrenia and a polymorphism close to the promoter site of the cytosolic phospholipase-A2 gene which is mapped to chromosome 1q25. The schizophrenic population was heterogeneous with regards age, symptoms severity and treatment. A significantly higher percentage concentration of dihomogamma-linolenic acid (DGLA) was found in the red cell membranes of schizophrenics compared to matched controls. All other fatty acids examined showed no difference from the normal population. No correlation was found between any demographic factor, treatment variable, diet, drug use, alcohol or tobacco consumption which could explain the biochemical findings. A negative correlation was found between the concentration of DGLA in red blood cell (RBC) membranes and severity of symptoms of schizophrenia. In particular, there was a significant correlation (r = -0.41, p = 0.009) between DGLA percentage concentrations and 'disorganised' symptoms. No association was found between schizophrenia and alleles of the polymorphism near the phospholipase-A2 gene or between fatty acid concentrations and the presence of any particular alleles. This study therefore finds support for membrane phospholipid abnormalities in patients with schizophrenia and particular symptom clusters, but does not replicate a previous report of an allelic association between a polymorphism close to the site of the cytosolic phospholipase-A2 gene and schizophrenia.     

Polyunsaturated fatty acids, Part 2: Biotransformations and biotechnological applications

The realization of the important biomedical roles of polyunsaturated fatty acids has led to the development of methods for obtaining and manipulating polyunsaturated lipids. Enzyme-mediated reactions have demonstrated unique advantages over chemical approaches and commercial lipase- and phospholipase-catalysed processes have been developed to address the mid- to high-value polyunsaturated-lipid market. Research over the past two decades has also highlighted the broad spectrum of bioactive products derived from the oxidation of polyunsaturated fatty acids. The potential of these compounds in the flavour, fragrance, pharmaceutical and fine-chemical arenas has encouraged the elaboration of biotransformation strategies based on isolated enzymes and whole cells.     

Calcium metabolism, osteoporosis and essential fatty acids: a review

Essential fatty acid (EFA)-deficient animals develop severe osteoporosis coupled with increased renal and arterial calcification. This picture is similar to that seen in osteoporosis in the elderly, where the loss of bone calcium is associated with ectopic calcification of other tissues, particularly the arteries and the kidneys. Recent mortality studies indicate that the ectopic calcification may be considerably more dangerous than the osteoporosis itself, since the great majority of excess deaths in women with osteoporosis are vascular and unrelated to fractures or other bone abnormalities. EFAs have now been shown to increase calcium absorption from the gut, in part by enhancing the effects of vitamin D, to reduce urinary excretion of calcium, to increase calcium deposition in bone and improve bone strength and to enhance the synthesis of bone collagen. These desirable actions are associated with reduced ectopic calcification. The interaction between EFA and calcium metabolism deserves further investigation since it may offer novel approaches to osteoporosis and also to the ectopic calcification associated with osteoporosis which seems to be responsible for so many deaths.     

Polyunsaturated fatty acids, Part 1: Occurrence, biological activities and applications

Polyunsaturated fatty acids form a unique class of food constituents that show a wide range of functions in biological systems. Investigations over the past two decades have uncovered their roles and those of their eicosanoid metabolites, and have highlighted their homeostatic functions in mammals. A growing number of common human medical conditions are thought to be traceable to dysfunctions in the eicosanoid system, which could in turn be due to imbalances in the intake and/or metabolism of polyunsaturated fatty acids. This, together with medical advances, has spurred the introduction of biomedical products, nutritionals, fortified foods and health supplements.