Epidemiology applied to the investigation of infant health determinants: basic concepts and methods

Epidemiologic principles and methods have been widely employed in clinical research. The purpose of this paper is to discuss basic epidemiological concepts applied to the investigation of the determinants of infant diseases. The theoretical framework outlines the hypothesis of the investigation. The design of the study is chosen accordingly. Exposure and outcome are defined, and the sampling criteria and the strategies for its implementation are specified. The researcher can be an observer (as in cross-sectional, cohort and case-control studies) or can determine who will be exposed in the experimental studies (clinical trials). Cross-sectional study is the easiest one to conduct, since exposure and outcome are assessed simultaneously in a well-defined population. In a cohort study, a group of people is assembled according to the exposure and followed over time to detect who will develop the outcome. In a case-control study,people are selected based on disease status. Then, they are investigated about previous exposures which could be associated with the development of the disease. The investigator allocates the exposure and then follows the participants to assess the outcome in clinical trials. Contrasting with the experiment developed in laboratory, the subjects are human beings.     

Zinc and copper in infants fed breast-milk or different formula

In 129 term infants at birth and at the age of 4 months, zinc and copper concentrations of plasma and urine were determined by graphite furnace atomic absorption spectrophotometry and the values correlated to other biochemical parameters and somatic data. Of the infants, 49 were exclusively breast-fed, 44 fed with various commercially available cow's milk formula, 35 fed with a hypollergenic formula (cows's milk whey hydrolysate, commercially available, supplemented with zinc and copper). Plasma zinc values declined from birth to the age of 4 months in all three groups (P<0.001). In formula fed children, 4 months old, the values (11.1±1.7 mol Zn/l) were significantly lower than in breast-fed (12.2±1.7 mol Zn/l;P=0.004) or babies on hypo-allergenic formula (12.4±1.6 mol Zn/l;P=0.0015). In accordance with the literature plasma copper and caeruloplasmin values increased significantly within the first 4 months of life, the plasma levels were similar in either feeding group, only urinary copper excretion was higher in male infants on hypoallergenic formula (P<0.03) at the age of 4 months. There were no correlations between zinc or copper values and alkaline phosphatase. In infants on hypo-allergenic formula there was a negative correlation between plasma zinc and weight or height increments. Despite different zinc and copper supply, presumedly different bioavailability, and different plasma zinc values, all infants thrived and weight and length increments were similar in each group.     

Characterization of mechanical withdrawal responses and effects of mu-, delta- and kappa-opioid agonists in normal and mu-opioid receptor knockout mice

Clinical and experimental observations suggest that opiates can exert different influences on the perception of stimuli from distinct sensory modalities. Thermally-induced nociception is classically responsive to opiate agonists. mu-Opioid receptor-deficient transgenic mice are more sensitive to thermal nociceptive stimuli and morphine fails to attenuate the nociceptive responses to thermal stimuli in these animals. To enhance our understanding of opiate influences on mechanical sensitivity, we have examined withdrawal responses to a sequence of ascending forces of mechanical stimuli in mice with normal (wild type), half-normal (heterozygous) and absent (homozygous) mu-opioid receptor levels. We report data from mice examined without drug pretreatment or following pretreatment with morphine, the selective kappa-opioid agonist, U50488H, and the selective delta-opioid agonist, DPDPE. Saline-pretreated mice of each genotype displayed similar, monotonically increasing frequency of withdrawal responses to the graded stimuli. Subcutaneously administered morphine produced a dose-dependent reduction in withdrawal responses in wild type and heterozygous mice, but had no significant effect in homozygous mice. Intraventricular administration of DPDPE also reduced the frequency of paw withdrawal (FPW) in wild type mice, but not in homozygous mice. In contrast, systemic U50488H produced a dose-dependent attenuation of paw withdrawal in both wild type and homozygous mice. These findings suggest that (1) interactions of endogenous peptides with mu-opioid receptors may not play a significant role in the response to mechanical stimuli in drug-free animals, and (2) deficiency of mu-opioid receptors has no functional consequence on the response to the prototypical kappa-opioid receptor agonist, but decreases responses to the prototypical mu- and delta-opioid receptor agonists.     

Patterns of relation and premorbid personality in late paraphrenia and depression

38 patients with late paraphrenia and 38 with endogenous depression of late onset were compared regarding interpersonal relations and personality traits by means of semistructured interviews. The prevalence of premorbid personality disorder was determined by the Structured Clinical Interview for DSM-III-R Personality Disorders. The main objective of the study was to look for lifetime relation patterns and personality traits distinguishing the two groups and pointing to a specific premorbid vulnerability of paranoid and depressive patients. A high rate of personality disorder comorbidity was found in both groups, with mainly paranoid and schizoid disorder in late paraphrenic patients (39%) and avoidant, dependent or compulsive personality in depressives (35%). As a rule, this corresponded to a lifelong pattern of seclusion and self-sufficiency in the paranoid, and of close intimacy and heteronomy in the depressive patients. On the basis of the results, a polar typology of personality and interpersonal relations in both patient groups is developed.     

Value of alignment osteotomy of the proximal tibia in the endoprosthesis period]

AIM OF THE STUDY: To evaluate the value of high tibial osteotomy in times of growing numbers of endoprostheses we compared our personal with other results of this method as well as of the unilateral sledge prosthesis. MATERIAL AND METHODS: Between 1972 and 1993 the high tibial osteotomy as described by Coventry was performed in 105 patients. 98 patients could be examined clinically-radiologically and evaluated with a questionnaire. The indication for surgery was given in patients with unilateral arthrosis without affection of the retropatellar joint and without significant ligamentous instability. The varus deviation was in no case more than 10 degrees. The average follow-up for the clinical-radiologic examination was 9.4 years. RESULTS: 77 patients (78.6%) were satisfied with the outcome of the surgery. Here it was seen that neither age nor pain or instability had an influence on this judgement. The walking distance on the other hand had a significant influence. Stair climbing and range of motion were significantly important as well. 23 patients gave the judgement "excellent", 31 "good", 36 "satisfactory" and 8 patients were "not satisfied". A significant influence of patient age on the judgement could not be proven. The division in the Japanese Score showed "good" results in 14%, "moderate" in 81% and "poor" in 5%. 13 knee joints (13.3%) were absolutely pain-free and in 67 cases (68.4%) there were a definite pain reduction. A significant correlation between the preoperative axis deviation and pain could not be found. An average flexion of 97.5 degree and an extension deficit of 3.3 degree on average was seen. A significant difference of range of motion dependent on age groups could not be found. In 42 knees (42.9%) the lateral ligaments were clinically stable, in 35 cases (35.7%) there was a first degree lateral stress gap and in 21 cases (21.4%) there was a second degree lateral instability. A significant correlation between the instability and age or pain could not be proven. 13 revision surgeries including 9 endoprosthesis implantations were performed. CLINICAL RELEVANCE: The study showed a high level of satisfaction with an exact surgical indication. When seeing the growing number of implanted uni- or tricompartmental endoprostheses the procedure of tibial osteotomy can be suggested for patients with unilateral arthrosis without retropatellar arthrosis, with an axis deviation less than 15 degrees, with unaffected cartilage of the contralateral compartment and without ligamentous insufficiency independent of patient age.     

Effect of patient age on use of the knee joint score

AIM OF THE STUDY: Clinical studies are done with the help of scores though different factors of influence lower comparability. The underlying study examines the influence of patient age as this always presents a certain span. METHOD: 96 degree I damaged knee joints were examined by 3 examiners using the Larson-, Lysholm-, Marshall-, HSS- and OAK-score. Furthermore ratings by a VAS and the Tegner activity score were done. With the Friedman test, the rank correlation coefficient by Spearman and the contingency chart by Bowker it was tested if the examiners and the scores rate equally. To find out the influence of the age three age groups were made up. RESULTS: The examiners judged significantly different excluding the Marshall and the OAK scores. In between two examiners no significant difference could be found between the young and the middle-aged patient group. Between two other examiners no significant difference was found only for the Lysholm and the HSS score in the young group and only for the Lysholm score in the middle-aged group. In the group of the senior patients no significant difference for the scores by Lysholm, Marshall and OAK were found. In the comparison of the second examiner pair no significant differences could be proven by the scores by Larson, the OAK and the HSS. All other comparisons were significantly different. In the comparison of all five scores significant differences were seen between the Larson score and the HSS and the Lysholm and the HSS. The Lysholm score proved to be the strictest, the HSS to be the leanest. CONCLUSION: Especially for the senior patients in dependency of the examiner and the chosen score significant differences were found concluding that the relevance of results lessens for future times as the score results drop with patient age anyway. The age span in one study should have a maximum of 10-20 years to reduce the influence of age on the final result.     

A cross-sectional study of workers in the chemical industry with occupational exposure to hexamethylenetetramine

Objectives: To assess the health effects of hexamethylenetetramine (HMT) on the airways and the skin of workers in the chemical industry. Methods: A cross-sectional study was performed with 17 employees of a HMT-producing chemical plant and 16 control subjects from the plant. In addition, we examined 4 out of 5 subjects who had left the production for medical reasons during the last 10 years. Anamnestic data, total and specific IgE to four environmental allergens, lung function and bronchial responsiveness to methacholine were assessed by standard procedures. Skin prick tests (SPT) and patch tests were performed with known sensitizing substances and HMT 100 mg/ml and 2% pet and aq. Results: A high number of exposed subjects and controls reported symptoms during the previous year (64.7% vs 68.8%), most of them were not related to work. Work-related symptoms and objective parameters did not show differences between groups. No sensitizations to HMT as assessed by SPT or patch tests were found. Among those who had left the HMT production for medical reasons, 2 former baggers showed sensitizations to HMT by patch tests. These reported eczema during exposure but lost symptoms after removal from exposure. Geometric mean HMT concentrations as assessed by personal sampling were 0.3 [95% confidence intervals (CI) 0.1; 0.9] mg/m³ in shiftleaders and 0.6 (95% CI 0.3; 1.1) mg/m³ in baggers. Conclusion: High exposures to HMT may cause allergic contact dermatitis. There was no evidence of an increased risk for occupational asthma at mean airborne HMT concentrations below 1 mg/m³. Received: 4 February 1999 / Accepted: 10 July 1999     

Methods of measuring susceptibility of anaerobic bacteria to trovafloxacin,including quality control parameters

Three methods approved by the National Committee for Clinical Laboratory Standards for testing the susceptibility of anaerobic bacteria were used to evaluate the fluoroquinolone, trovafloxacin. The methods gave essentially comparable results with 126 anaerobes and with three quality control strains. A collaborative study defined the quality control range for trovafloxacin MICs. Trovafloxacin had good in vitro activity against the more common anaerobes (MIC 90 <- 2.0 (g/ml).Trovafloxacin (CP-99,219) is a fluoroquinolone with a broad spectrum of antibacterial activity (1–3). Its in vitro spectrum includes many anaerobic bacteria (4).The National Committee for Clinical Laboratory Standards (NCCLS) currently recommends three different methods for testing the susceptibility of anaerobic bacteria (5). The standard reference method is an agar dilution procedure using Wilkins-Chalgren agar. Two alternative methods are an agar dilution technique using Brucella blood agar and a microdilution procedure using a broth version of Wilkins-Chalgren medium. It is important to determine whether these three procedures actually produce identical test results with each antimicrobial agent likely to be tested against anaerobes.     

Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes

The efficacy and tolerance of orally administered vinpocetine was investigated in patients suffering from mild to moderate organic psychosyndromes including primary dementia. Two hundred and three patients were included in a placebo-controlled, randomized double-blind, multicentre trial and received every day for 16 weeks either: 3 x 10 mg doses of vinpocetine, 3 x 20 mg doses of vinpocetine, or 3 x placebo. Patients were assessed on ratings of clinical global impression, cognitive performance and on measures of the quality of life including depressive illness. There were no clinically relevant side-effects reported and the frequencies of adverse events between patients treated with vinpocetine (30 mg or 60 mg) and placebo were comparable. Statistically significant improvements were found in favour of both active treatment groups compared to placebo in both confirmatory evaluations of efficacy of treatment: the "Global Improvement" (on the CGI scale) and cognitive performance (SKT). Vinpocetine was also superior to placebo in ratings of the "severity of illness". This study demonstrates the usefulness and efficacy of vinpocetine in the management of patients with moderate organic psychosyndromes. An apparently greater therapeutic efficacy of 3 x 10 mg vinpocetine compared with the higher vinpocetine dosage is statistically not significant.