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Influence of alprazolam on opioid analgesia and side effects during steady-state morphine infusions.

The primary purpose of this study was to examine whether alprazolam pretreatment can increase the analgesic potency of morphine without increasing opioid side-effect intensities. We employed computer-controlled, variable-rate morphine infusions based on each subject's pharmacokinetic profile for morphine derived from a tailoring bolus dose of the drug administered 1 or 2 weeks before the infusion test sessions. On each of 2 test days, we used dental electrical stimulation to determine stimulus intensity that produced consistent reports of strong (but tolerable) pain; this intensity was used for the rest of that session. Then, we measured baseline (no drug) pain intensity reports, pain-related evoked potentials recorded from vertex, and other parameters typically affected by opioids (subjective side effects). We administered alprazolam (1 mg) or placebo (lactose) orally to the subject and then repeated the test battery 30 min later. One hour after the alprazolam or placebo dose, we initiated the tailored morphine infusion to reach target plasma morphine concentration plateaus of 16, 32 and 64 ng/ml (45-min duration each) on both test days. The test battery used during baseline was then repeated at each target concentration plateau. The order of alprazolam versus placebo pretreatments was counterbalanced across subjects and known only to the investigator operating the infusion system. Results suggest that alprazolam at the dose studied did not alter analgesic potency of morphine. However, alprazolam did clearly decrease the intensity of nausea reported by subjects during and after termination of the morphine infusions. Of special interest, alprazolam alone (30 min after oral dosing) decreased evoked potential amplitude consistently without affecting pain intensity reports.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Infantile colic. Association with lactose and milk intolerance.

Intolerance to lactose and cow's milk protein was prospectively evaluated in 56 infants with apparent colic. A complete blood cell count, sedimentation rate, test for quantitative IgE level, radioallergosorbent test (performed in 15 patients), and at least three stool examinations for pH, presence of reducing substances, and occult blood were performed in 56 infants (46, appropriate size for gestational age; ten, small for gestational age) and results were within normal limits for age. This study suggests that tolerance to lactose and cow's milk protein does not have a significant role in infantile colic.

Animals↗

Halophilic Vibrio species isolated from blood cultures.

The Special Bacteriology Section of the Center for Disease Control has received 38 cultures of a halophilic bacterium which apparently unnamed. On the basis of the minimal characteristics of Vibrio species proposed by Hugh and Sakazaki, this bacterium belongs to the genus Vibrio. The unnamed species can be differentiated from Vibro parahaemolyticus by a lower tolerance for sodium chloride (NaC1) and the fermentation of lactose. The failure to ferment sucrose is an additional characteristic which differentiates these organisms from V. alginolyticus. Of 33 unnamed species strains tested, all were sensitive to penicillin, ampicillin, carbenicillin, cephalothin, chlorapmphenicol, gentamicin, tetracycline, rifampin, nitrofurantoin, and sulfisoxazole by agar diffusion and agar dilution tests. The sources of isolation of the cultures of the unnamed species suggest that it is a clinically important organism. Twenty strains were isolated remaining cultures were isolated from localized infections of the extremities. In contrast, only 2 of 60 cultures of V. parahaemolyticus and V. alginolyticus received in our laboratory as human isolates from extra-intestinal sources were isolated from blood.

Anti-Bacterial Agents↗

Lactose digestion from flavored and frozen yogurts, ice milk, and ice cream by lactase-deficient persons.

Lactose digestion from and tolerance to flavored and frozen yogurts, ice cream, and ice milk were evaluated (20 g lactose/meal) in lactase-deficient subjects by use of breath hydrogen techniques. Unflavored yogurt caused significantly less hydrogen production than milk (37 vs 185 delta ppm X h, n = 9). Flavored yogurt was intermediate (77 delta ppm X h). Subjects were free of symptoms after consuming flavored and unflavored yogurts. Of seven commercial yogurts tested, all contained significant levels of microbial beta-galactosidase (beta-gal). In addition, eight subjects were fed meals of milk, ice milk, ice cream, and frozen yogurts with and without cultures containing high levels of beta-gal. Peak hydrogen excretion after consumption of frozen yogurt with high beta-gal was less than one-half of that observed after the other five test meals and intolerance symptoms were absent. Tolerance to frozen yogurt, produced under usual commercial procedures, was found to be similar to that of ice milk and ice cream.

Adult↗

Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect?

BACKGROUND: Uncontrolled studies of lactose intolerant subjects have shown that symptom severity decreases after chronic lactose consumption. Adaptation of the colonic flora might explain this improvement. AIMS: To compare the effects of regular administration of either lactose or sucrose on clinical tolerance and bacterial adaptation to lactose. METHODS: Forty six lactose intolerant subjects underwent two 50 g lactose challenges on days 1 and 15. Between these days they were given 34 g of lactose or sucrose per day, in a double blind protocol. Stool samples were obtained on days 0 and 14, to measure faecal beta-galactosidase and pH. Symptoms, breath H2 excretion, faecal weight and electrolytes, and orofaecal transit time were assessed. RESULTS: Except for faecal weight, symptoms were significantly milder during the second challenge in both groups, and covariance analysis showed no statistical difference between them. In the lactose group, but not in the sucrose group, faecal beta-galactosidase activity increased, pH dropped, and breath H2 excretion decreased. CONCLUSION: Bacterial adaptation occurred when lactose intolerant subjects ingested lactose for 13 days, and all symptoms except diarrhoea regressed. Clinical improvement was also observed in the control group which displayed no signs of metabolic adaptation. This suggests that improved clinical tolerance may be just a placebo effect.

Adult↗

Deoxyribonucleic acid base composition of some members of the Micrococcaceae.

Auletta, Angela E. (Catholic University, Washington, D.C.), and E. R. Kennedy. Deoxyribonucleic acid base composition of some members of the Micrococcaceae. J. Bacteriol. 92:28-34. 1966.-Thirty-seven strains from the genera Micrococcus, Staphylococcus, Gaffkya, and Sarcina were examined for deoxyribonucleic acid base composition and biochemical activity. Organisms were tested for production of catalase, coagulase, deoxyribonuclease, oxidase, phosphatase, hydrogen sulfide, indole, and acetoin; nitrate reduction; gelatin, starch, and urea hydrolysis; citrate and ammonium phosphate utilization; NaCl tolerance; growth at 10 and 45 C, and growth in litmus milk. They were tested for production of acid from dextrose and mannitol under anaerobic conditions, and for aerobic production of acid from dextrose, mannitol, lactose, sucrose, raffinose, maltose, xylose, and glycerol. Organisms could be divided into two groups on the basis of guanine-cytosine (GC) content. Group I had an average GC content of 32%, and included all organisms which produced acid from dextrose. Group II had an average GC content of 62%, and included those organisms incapable of producing acid from dextrose under anaerobic conditions. Sarcina ureae had a GC content of 43%.

Carbohydrate Metabolism↗

Optimisation of initial cell concentration enhances freeze-drying tolerance of Pseudomonas chlororaphis.

The freeze-drying tolerance of Pseudomonas chlororaphis, an antifungal bacterium used as biocontrol agent was investigated. P. chlororaphis is freeze-drying sensitive and the viability drops more than 3 log units in the absence of protective freeze-drying medium. Of the freeze-drying media tested, lactose, sucrose, trehalose, glutamate, sucrose with glutamate, skimmed milk, and skimmed milk with trehalose, skimmed milk gave the lowest survival (0.6+/-0.2%) and sucrose the highest (6.4+/-1.2%). Cellular accumulation of sucrose from the freeze-drying medium and the protective effect of sucrose were dependent on sucrose concentration. The effect of initial cell concentration, from 1 x 10(7) to 5 x 10(10) CFU/ml, on survival after freeze-drying was studied for carbon starved cells with sucrose as freeze-drying medium. The highest freeze-drying survival values, 15-25%, were obtained for initial cell concentrations between 1 x 10(9) and 1 x 10(10) CFU/ml. For cell concentrations outside this window more than 10 times lower survival values were observed. P. chlororaphis was cultivated to induce stress response that could confer protection against freeze-drying inactivation. Carbon starvation and, to a lesser extent, heat treatment enhanced freeze-drying tolerance. By combining optimal cell concentration, optimal sucrose concentration and carbon starvation the survival after freeze-drying was 26+/-6%.

Animals↗

Yogurt--an autodigesting source of lactose.

Large quantities of yogurt are consumed by some lactase-deficient population groups. We used breath hydrogen measurements to determine whether lactase-deficient subjects absorbed lactose in yogurt better than lactose in milk. Ingestion of 18 g of lactose in yogurt resulted in only about one third as much hydrogen excretion as a similar load of lactose in milk or water, indicating a much better absorption of lactose in yogurt. Ingestion of yogurt also resulted in fewer reports of diarrhea or flatulence than did a similar quantity of lactose ingested in milk or a water solution. The enhanced absorption of lactose in yogurt appeared to result from the intraintestinal digestion of lactose by lactase released from the yogurt organisms. This autodigesting feature makes yogurt a well-tolerated source of milk for lactase-deficient persons and may explain the widespread consumption of yogurt by lactase-deficient population groups.

Adult↗

The effect on motion sickness and oculomotor function of GR 38032F, a 5-HT3-receptor antagonist with anti-emetic properties.

1. The 5-hydroxytryptamine (5-HT3) receptor antagonist, GR 38032F, which possesses potent anti-emetic properties in vomiting induced by cancer chemotherapeutic drugs, has been tested to determine its value in the prophylaxis of motion sickness induced by cross-coupled stimulation. The double-blind trial compared GR 38032F with both a placebo (lactose) and with hyoscine. In addition, studies of ocular pursuit and saccadic eye movements were carried out following the administration of each drug. 2. The prophylactic effect of GR 38032F on motion-induced nausea was indistinguishable from that of placebo, whereas following hyoscine subjects showed a highly significant (P less than 0.001) increase in tolerance to cross-coupled stimulation. Tests of oculomotor function showed no effect on saccadic eye movement from either drug. However, both drugs produced a significant (P less than 0.05) though small reduction in eye velocity gain during pursuit eye movement. 3. These findings suggest that the 5-HT3 receptor is not involved in the neural pathways that bring about motion sickness, but that it may have a role in the control of ocular pursuit. The absence of an anti-motion sickness effect from a drug that is effective in the treatment of vomiting induced by cancer chemotherapy serves to emphasize that different neural mechanisms are involved in the generation of motion sickness.

Adolescent↗

Insulin resistance, hyperglycemia, glucosuria, and galactosuria in intensively milk-fed calves: dependency on age and effects of high lactose intake.

Calves intensively fed milk replacers frequently develop postprandial insulin resistance, characterized by excessively elevated plasma insulin concentrations, hyperglycemia, and glucosuria. To test the hypothesis that insulin secretion and insulin-dependent dependent glucose metabolism are modified by age and carbohydrate intake, 20 male calves (Simmental x Red Holstein) were fed a milk replacer containing 290 and 423 g lactose/kg DM from 60-70 to 190-200 kg BW. Responses of insulin and glucose to milk replacer intake and orally administered glucose and pre- and postprandial glucose responses to i.v. infused glucose and i.v. injected insulin were tested at 75-105 and 160-200 kg BW. Urine was collected during 24h to determine glucose, galactose, dopamine, noradrenaline, and creatinine excretion. Insulin resistance, hyperinsulinemia, hyperglycemia, glucosuria, and galactosuria developed with increasing age and occurred primarily postprandially. High lactose intake enhanced postprandial hyperglycemia but did not significantly increase glucosuria, galactosuria, and hyperinsulinemia. Based on urinary excretion of dopamine and noradrenaline there was a marked age-dependent increase in the activity of the sympathetic nervous system, which was not modified by lactose intake. high feeding intensity and lactose intake, excessive hyperinsulinemia per se and enhanced activity of the sympathetic nervous system possibly contributed to the development of insulin resistance. Glucose-dependent insulinotropic polypeptide, growth hormone and cortisol concentrations, and iron intake were low and comparable in both groups and therefore were etiologically not involved in the development of insulin resistance. Increasing circulating concentrations of insulin-like growth factor I during growth may have in part allowed high growth rates in the presence of insulin resistance.

Aging↗

[Hydrogen (H2) breath tests in the diagnosis of small intestine diseases].

We have applied the ion sensitive analysis of hydrogen (H2) in expired air in intervals of five minutes for five hours to determine carbohydrate malabsorption. In 19 patients with lactose malabsorption the increase in hydrogen was prior (45, SE 13 min) to healthy volunteers (142, SD 71 min, p less than 0.01). In comparison to blood glucose with the breath test no false positive results were observed. D-xylose absorption measured by breath test and renal excretion for five hours was determined in 24 volunteers and 12 patients with various intestinal diseases. There was a good correlation between both methods. In all patients the area under the concentration-time-curve was elevated (2077, SD 1260 ppm H2/5h) compared to healthy volunteers (434, SD 271 ppm H2/5h, p less than 0.01). Small bowel transit time was determined by ingestion of lactulose. In 32 healthy persons transit time was 85, SD 19 min. In 10 patients an early increase in hydrogen indicated bacterial overgrowth in the small bowel while 14C-Cholylglycine-breath test was abnormal in only six patients. The hydrogen breath test measured by ionsensitive mode is noninvasive, well tolerated, semiquantitative, and ideally suited for screening of intestinal disorders.

Adult↗

Subchronic oral toxicity studies with gamma-cyclodextrin in rats.

The toxicity of gamma-cyclodextrin (gamma-CD), a cyclic polymer of eight alpha-1,4-linked glucopyranosyl units with potential applications as a food ingredient, was examined in a 2-week pilot study followed by a 13-week oral toxicity study in Wistar rats. In the 2-week study, the test substance was administered to groups of 5 male rats at dietary levels of 0, 5, 10, 15, and 20%. In the 13-week study, groups of 20 rats/sex received diets with 0, 1.5, 5, or 20% gamma-CD. In each study, a comparison group receiving a diet with 20% lactose also was included. The 13-week study also included satellite groups of 10 rats/sex for the control and 20% gamma-CD groups. These satellite groups were kept on a standard, cereal-based rodent diet for a 4-week recovery period after termination of the treatment period. Parameters measured during the two studies were clinical signs, body weights, food and water intake, clinicochemical parameters, organ weights, and gross observation at necropsy. In the 13-week study, ophthalmoscopic and hematological examinations, urine and feces analyses, and histopathological examination of standard organs and tissues were conducted. There were no treatment-related mortalities in either study. Soft stools and, in the 13-week study, infrequent occurrences of diarrhea were noted in the lactose group at the beginning of treatment. Among the gamma-CD groups, soft stools occurred in only a few animals of the high-dose groups (>/=10% gamma-CD) during the first few days of treatment. Mean body weights tended to be slightly reduced in males of the 20% gamma-CD and 20% lactose groups. However, food efficiency was not affected by treatment except in the 13-week study in males of the 20% gamma-CD group during the first week of treatment. The hematological examinations and the semiquantitative urinalyses (conducted in the 13-week study) and the clinicochemical investigations (both studies) did not reveal any changes that could be attributed to gamma-CD treatment. Except for a slight cecal enlargement, which is commonly observed in rodents upon ingestion of incompletely absorbed carbohydrates, organ weights did not exhibit relevant changes as a result of gamma-CD treatment. On histopathological examination (13-week study), no treatment-related abnormalities were found. In conclusion, the ingestion of gamma-CD for 13 weeks at dietary levels of up to 20% (corresponding to intakes of 11.4 and 12.7 g/kg body wt/day for male and female rats, respectively) was well tolerated and did not produce any signs of toxicity.

Administration, Oral↗

Glucose and insulin metabolism in ruminating and veal calves fed high and low fat diets.

Holstein male calves were maintained on conventional (milk to 6 wk of age, fed grain and hay after weaning) and veal (milk replacer only) diets to 16 wk of age. Within each of these 2 physiological states (ruminating or non-ruminating), calves were fed low or high fat diets (ruminating: 3 and 10%; veal: 10 and 18%). Glucose tolerance tests were undertaken at 8 and 16 wk of age in each group. Basal concentrations (4 hr postfeeding) and areas under the response curves for plasma glucose and insulin were higher in veal calves (P < .0001). Ruminating calves fed higher fat utilized glucose more readily (smaller areas under the curves for both glucose and insulin, P < .10) than those fed lower fat. Age did not influence basal glucose concentrations (P > .10), but older calves had higher basal insulin (P < .0001) and greater areas under the curves (P < .0005) for both glucose and insulin after a glucose challenge. Rate of clearance (k) was greater in ruminating calves (P < .001). Though rate of clearance in veal calves was slower, larger plasma pool size caused veal calves on average to utilize glucose at a 15% greater rate per kg body weight than ruminating calves. Whereas fat concentration in the diets did not influence glucose metabolism in veal calves, the high lactose content (> 50% of diet dry matter) of veal diets induced severe insulin resistance in these calves.

Animals↗

Adult-type hypolactasia and calcium availability: decreased calcium intake or impaired calcium absorption?

UNLABELLED: Adult-type hypolactasia, as mediated by a widespread genetic predisposition, not only reduces calcium intake but also calcium absorption in the presence of high amounts of lactose and may, therefore, promote osteoporosis. A lactose-reduced diet and lactose-free calcium supplements may reverse this imbalance. INTRODUCTION AND HYPOTHESIS: Adult-type hypolactasia (HL) defined by the LCT(-13910) polymorphism may reduce calcium intake by reducing dairy consumption and, therefore, promote osteoporosis. This study aimed to evaluate whether lactose also decreases intestinal calcium absorption in subjects with HL and whether lactose-reduced diet and lactose-free calcium supplementation as recommended could maintain bone mineral density (BMD). METHODS: Based on LCT genotyping, 73 postmenopausal women with and without HL underwent a conventional H(2) breath test with a concomitant oral strontium absorption test lasting 150 minutes, which closely reflects intestinal calcium absorption. In addition, we compared bone-specific laboratory parameters, lumbar and femoral BMD, and spinal radiographs to a similar bone assessment 5 years earlier. RESULTS: LCT genotyping and functional lactose malabsorption tests were highly correlated. Dairy product consumption was reduced by 80% in HL individuals. During concomitant lactose application, mean strontium absorption was blunted by 54% in HL subjects after 150 minutes (1272 +/- 629 microg/L vs. 2020 +/- 1130 microg/L in lactose tolerant subjects, p=0.001). Nevertheless, BMD in HL subjects remained stable with lactose-free calcium supplements during the observation period. CONCLUSION: Both decreased calcium intake as well as lactose-associated impaired calcium absorption may predispose subjects with HL to osteoporosis. Lactose-free calcium supplementation may help to maintain BMD in HL subjects.

Absorption↗

Milk tolerance and the malnourished African.

Adult (primary) lactose malabsorption is practically universal in Africans of Bantu and San ('Bushmen') stock. Recent environmental changes, especially in rural areas, have exacerbated rates of malnutrition in hospital patients belonging to these groups. In order to assess the advisability of using milk as a nutritional supplement for such patients, the tolerance and absorption of 350 ml boluses of whole milk (containing 17 g lactose) was measured in 110 malnourished hospitalized patients in Namibia and South Africa belonging to Bantu (ie, Zulus, Hereros, and Kavangos) and San (ie, Bushmen) populations and compared with 22 healthy Westernized controls. Mild symptoms of intolerance were noted in about 10 per cent of Bantus and 20 per cent of Bushmen in comparison to 33 per cent of lactose-malabsorbing controls consuming Westernized diets and reported rates of 48 and 80 per cent in American population studies. The average increase in breath hydrogen excretion of 20 parts per million was also lower than the value of 34 parts per million in controls. Fasting breath methane concentrations were high in between 60-84 per cent of the groups of patients, but the level was not significantly affected by milk ingestion. Despite the combination of hypolactasia and malnutrition, 350 ml drinks of milk were well tolerated by African patients. Thus, milk should form an appropriate nutritional supplement for Africans hospitalized in rural areas.

Africa↗

[Lactose intolerance. Its definition, its prevalence in Mexico, and its implications in milk consumption].

In this document we describe some aspects of lactose and milk intolerance, discuss the results of studies carried out previously in Mexico, and report an investigation whose objective was to quantify the impact of lactose intolerance on the habitual consumption of milk in an open population. The prevalence of lactose intolerance and its effect on the consumption of milk was studied in three regions of Mexico. The design of the study was prospective, randomized, double-blind and crossover. The presence of milk intolerance was investigated in 960 subjects with ages between 6 months and 99 years who, as a function of age, received 240 or 360 mL of intact milk and the same amount of hydrolyzed milk. We quantified the consumption of milk and the presence of symptoms after ingesting the tested milk. Seven percent manifested symptoms with the intact milk but only 2% with the hydrolyzed milk (p < 0.001). The presence of symptoms in the intolerant subjects was significantly associated with a lower consumption of milk in comparison with the tolerant individuals (p < 0.001). On the other hand, the consumption of milk appeared to be only marginally associated with the intolerance and its symptoms. We conclude that lactose intolerance does not appear to be a major factor in determining milk consumption in Mexican healthy populations.

Adolescent↗

A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?

Persistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism (C-13910T) in an enhancer element 13.9 kb upstream of the lactase gene (LCT). The -13910*T allele occurs at very high frequency in northern Europeans as part of a very long haplotype (known as A), and promotes binding of the transcription factor Oct-1. However, -13910*T is at very low frequency in many African milk drinking pastoralist groups where lactase persistence phenotype has been reported at high frequency. We report here for the first time, a cohort study of lactose digester and non-digester Sudanese volunteers and show there is no association of -13910*T or the A haplotype with lactase persistence. We support this finding with new genotype/phenotype frequency comparisons in pastoralist groups of eastern African and Middle Eastern origin. Resequencing revealed three new SNPs in close proximity to -13910*T, two of which are within the Oct-1 binding site. The most frequent of these (-13915*G) is associated with lactose tolerance in the cohort study, providing evidence for a cis-acting effect. Despite its location, -13915*G abolishes, rather than enhances Oct-1 binding, indicating that this particular interaction is unlikely to be involved in lactase persistence. This study reveals the complexity of this phenotypic polymorphism and highlights the limitations of C-13910T as a diagnostic test for lactase persistence status, at least for people with non-European ancestry.

Adult↗

Does low lactose milk powder improve the nutritional intake and nutritional status of frail older Chinese people living in nursing homes?

BACKGROUND: Malnutrition is prevalent among nursing home residents in Hong Kong. Nutrient dense oral supplements and yoghurt are unpopular among the Chinese older people because of their unfamiliar tastes and relatively high costs. Vitamin and mineral supplements do not address the problem of protein calorie undernutrition. Milk powder may be a suitable alternative supplement, but diarrhoea resulting from lactase deficiency is common in Chinese people. OBJECTIVE: We hypothesized that a low lactose milk powder would be better tolerated in Chinese nursing home residents and result in improvement in nutritional intake without reducing habitual intake. DESIGN: Forty-seven residents were randomized to receive milk powder twice daily, or no supplement for seven weeks. Twenty-four hour food record, body weight, upper limb skinfold thicknesses and midarm circumference, grip strength, Barthel Index, and abbreviated mental test score were carried out at baseline and at seven weeks. RESULTS: The overall compliance was nearly 100%, and no subjects developed diarrhoea. Compared with controls, milk supplementation increased intake of calcium, vitamin D, vitamin A, riboflavin and potassium. There was no significant reduction in habitual dietary intake in supplemented subjects. There was a trend of weight gain in supplemented subjects, though this did not reach statistical significance. There was no change in handgrip strength, mental function and disability level. CONCLUSION: The study shows that low lactose milk powder is a well-accepted nutritional supplement without reducing habitual dietary intake.

Aged↗