Prognosis of functional recovery 1 year after hip fracture: typical patient profiles through cluster analysis.

BACKGROUND: Many investigators have identified distinct medical, demographic and psychosocial prefracture conditions that influence the functional outcome of patients surgically treated for a fracture of the hip. However, to design efficient intervention care programs addressing the needs of these patients, at optimal economic and social costs, more information is required on the typical combinations of prognostic determinants actually encountered. METHODS: Data on specific descriptors of the prefracture status and on mobility and functioning 1 year after surgical intervention were collected by interview from 253 consecutive patients hospitalized for a fracture of the proximal femur. Cluster analysis was used to form homogeneous groups of patients with similar profiles in terms of the 13 predictive variables and the 7 outcome variables significantly interrelated. The modeling procedure generated four clusters of patients with a typical profile sharply contrasted by their structure. RESULTS: Subjects of two clusters could walk without difficulty and were functionally independent prior to their hip fracture. One year later, however, mobility and functioning were only fully recovered by the members of one cluster. The majority of predictors were of less favorable prognostic value for the members of the second cluster. The other two clusters regrouped patients with impaired prefracture mobility that were either unaltered or even aggravated 1 year later. CONCLUSIONS. Cluster analysis identified typical profiles of elderly hip fracture patients. Close scrutiny of their respective global structure, in terms of combined prognostic determinants and outcomes, may help to develop specific management strategies that are more efficiently adapted to these different groups of patients.

Promotion of fibroblast adhesion by triple-helical peptide models of type I collagen-derived sequences.

The dissection of the activities mediated by type I collagen requires an approach by which the influence of triple-helical conformation can be evaluated. The alpha 1 beta 1 and alpha 2 beta 1 integrin binding sites within type I collagen are dependent upon triple-helical conformation and contained within residues 14-822 from alpha 1(I). Seven alpha 1(I)-derived triple-helical peptides (THPs) were synthesized based on charge clustering (alpha 1(I)256-270, alpha 1(I)385-396, alpha 1(I)406-417, alpha 1(I)415-423, alpha 1(I)448-456, alpha 1(I)496-507, and alpha 1(I)526-537). Three additional THPs were synthesized (alpha 1(I)85-96, alpha 1(I)433-441, and alpha 1(I)772-786) based on previously described or proposed activities (Kleinman, H. K., McGoodwin, E.B., Martin, G. R., Klebe, R. J., Fietzek, P. P., and Wooley, D. E. (1978) J. Biol. Chem. 253, 5642-5646; Staatz, W. D., Foik, K. F., Zutter, M. M., Adams, S. P., Rodriquez, B. A., and Santoro, S. A. (1991) J. Biol. Chem. 266, 7363-7367; San Antonio, J. D., Lander, A. D., Karnovsky, M. J., and Slayter, H. S. (1994) J. Cell Biol. 125, 1179-1188). Of the ten THPs, alpha 1(I)772-786 THP had the greatest activity, with half-maximal normal dermal fibroblast adhesion occurring at a peptide concentration of 1.6 microM. Triple-helicity was essential for activity of this sequence, as the non-triple-helical peptide analog (alpha 1(I)772-786 SSP) exhibited considerably lower levels of cell adhesion promotion even at peptide concentrations as high as 100 microM. Within the sequence itself, residues 784-786 (Gly-Leu-Hyp) were important for cellular recognition, as the alpha 1(I)772-783 THP had greatly reduced cell adhesion activity compared with alpha 1(I)772-786 THP. Preliminary studies indicate that the beta 1 integrin subunit mediates fibroblast adhesion to alpha 1(I)772-786 THP. The identification of fibroblast integrin binding sites within type I collagen may have important implications for understanding collagen metabolism.

Purification and analysis of synthetic, triple-helical "minicollagens" by reversed-phase high-performance liquid chromatography.

To better study collagen-mediated cellular and enzymatic activities, a generally applicable solid-phase methodology has been developed by which aligned triple-helical peptides (designated THPs or "minicollagens") ranging from 79 to 124 residues can be assembled. Reversed-phase HPLC is typically the purification method of choice following chemical synthesis of small proteins of this size, as well as one of the analytical techniques used to verify product purity. We have thus compared the effects of different stationary phases (C18, C4, or diphenyl), organic modifiers (acetonitrile or isopropanol), support pore sizes (120 angstroms, 300 angstroms, or nonporous), and counterions for the reversed-phase HPLC analysis of THPs. Large pore C18 or C4 reversed-phase HPLC gave broad peaks, resulting in poor resolution of the desired THP from synthetic impurities. Broad peaks were presumably due to conformational instability of THPs to reversed-phase conditions and subsequent slow cis-trans isomerization of the peptide bonds. Peak sharpness was improved greatly by use large-pore diphenyl reversed-phase HPCL. We found that THPs can be best resolved from synthetic impurities by diphenyl or non-porous C18 reversed-phase HPLC using water-acetonitrile gradients. These results most likely reflect conditions which maintain the native conformation of collagen-like triple-helices.

A fast protein liquid chromatography (FPLC) method for study of thyrotropin-releasing hormone (TRH) and its metabolite histidyl-proline diketopiperazine (CHP) in human blood: degradation in liver and pancreatic diseases.

We have developed a convenient method combining fast protein liquid chromatography (FPLC) with sensitive radioimmunoassay (RIA) for thyrotropin-releasing hormone (TRH) to separate and identify TRH and its metabolite histidyl-proline diketopiperazine (CHP) and applied this to study inactivation of TRH by blood extracts from patients with liver cirrhosis (LC) and acute edematous pancreatitis (AP). Blood samples spiked with TRH and CHP were extracted by cold methanol and injected on a reverse-phase FPLC column. A linear gradient was applied for separation. Subsequent analyses of fractions by RIA for TRH revealed that only fractions 9-10 contained TRH. Separation by retention time (9.9 +/- 0.8 min for TRH, 10.5 +/- 0.6 min for CHP, mean +/- SEM) was highly reproducible. For degradation studies, pooled sera from patients with LC and AP were incubated with TRH and CHP for 60 min. Inactivation of TRH was less rapid in the presence of blood extract from LC patients than that from normal subjects or AP patients. CHP was more stable than TRH. These data suggest that activity of TRH-degrading enzymes is reduced in liver disease, whereas it does not appear to be altered in AP. Degradation of CHP does not closely reflect metabolic processing of its major precursor. This rapid and sensitive method may be applicable for further investigations on the metabolism of TRH in organic fluids.

Evaluation of thyrotropin secretion before and after TRH by third generation chemiluminescent assay. Assessment of subclinical hyperthyroidism.

The recent introduction of third generation assays for TSH has led to a considerable improvement of assay sensitivity. To assess the clinical significance of subnormal basal TSH (b-TSH) values (< 0.2 microU/ml), we investigated b-TSH and TRH-stimulated TSH (r-TSH) by means of a new, highly sensitive immunochemiluminometric assay in 105 euthyroid subjects, 45 patients with overt hyperthyroidism and 18 patients suspected of having subclinical hyperthyroidism. A weak, albeit statistically significant, correlation (r = 0.48) was found between b-TSH and r-TSH and also between b-TSH and delta-TSH (r = 0.31) in euthyroid subjects. Consideration of b-TSH alone correctly identified 90 % of euthyroid subjects in this group; 10 of 105 apparently euthyroid subjects presented delta-TSH suggesting subclinical hyperthyroidism. While b-TSH was detectable (> 0.04 microU/ml) in 8 of 45 (18%) of hyperthyroid patients, all (100%) were abnormal in both b-TSH and r-TSH. 14 of 18 (78%) of patients with subclinical hyperthyroidism exhibited a blunted TSH response to stimulation (delta-TSH < 2 microU/ml). These results suggest that although the new generation of TSH assays can be a valuable addition to the diagnostic arsenal of thyroid function tests, certain limitations must still be accepted. Specifically, b-TSH in the "grey zone" (0.1-0.2 microU/ml) appears to be a less than reliable predictor of thyroid function.

[Postmortem diagnosis of cardiac amyloidosis in the aged. Anatomoclinical correlation]. / Diagnostic post-mortem de l'amyloïdose cardiaque du vieillard. Corrélation anatomoclinique.

The absence of specific clinical signs makes the diagnosis of cardiac amyloidosis difficult. Moreover, it is established that this condition, the prevalence of which increases with age, aggravates the prognosis of cardiac failure. The present study was undertaken to identify the clinical or paraclinical signs enabling more accurate diagnosis of this disease. Analysis of 2589 autopsy reports from the University Institutes of Geriatrics of Geneva between January 1972 and January 1990 recensed 58 cases of microscopic cardiac amyloidosis, but this diagnosis was not made in any of these patients before death. Of the potential indicators, the good specificity but poor sensitivity of atrial fibrillation and low voltage electrocardiogram was confirmed. On the other hand, the author's research found the association of radiological cardiomegaly and a raised erythrocyte sedimentation rate in nearly 70% of cases of cardiac amyloidosis with a false positive rate of only 10% in a control group.

[Prospective evaluation of specialized consultations in a geriatric university hospital]. / Evaluation prospective des consultations spécialisées dans un hôpital universitaire de gériatrie.

In a prospective study carried out over a 3 month period we analysed the views of consultants and residents taking part in 771 consultations to patients admitted to the Geriatric University Hospital of Geneva with the help of visual analogue scales. 27 medical subspecialties were involved. Both consultants and residents agreed that most of the consultations were useful for the elderly patient and for postgraduate teaching and learning. But the residents thought that consultations were more important for the patients' welfare than for the residents' education. Residents showed a tendency to underestimate crucial aspects of geriatric medicine (in particular the autonomy of the elderly patient) in preference to more "classical" medical preoccupations (diagnosis and treatment). Consultants were aware of the specificity of geriatric pathology but restricted their teaching during the intervention to what was requested by the resident.

[Micturition disorders following spinal anesthesia of different durations of action (lidocaine 2% versus bupivacaine 0.5%)]. / Miktionsstörungen nach Spinalanästhesie unterschiedlicher Wirkungsdauer (Lidocain 2% versus Bupivacain 0.5%).

Disturbances of micturition following spinal anaesthesia are considered to be rare and harmless side effects of this technique. For this reason, we set up a prospective study to investigate their incidence, characteristics and intensity. Our special interest was directed at the influence of the duration of action of local anaesthetics. METHODS. In a randomized, double-blind study, two groups, each consisting of 73 trauma surgical and orthopaedic patients, received isobaric spinal anaesthesia with either lidocaine 2% or bupivacaine 0.5%. From the 1st to the 3rd postoperative day, the patients were interviewed daily and asked specifically about disturbances of micturition. RESULTS. The two groups were comparable in terms of clinical data, spinal anaesthesia and surgery. Disturbances of micturition occurred only during the first 24 h and were observed in a total of 42%. They were about twice as frequent after bupivacaine (56%) as following lidocaine (27%). After bupivacaine there was a higher rate of difficult micturition or complete inability to micturate in the presence of an urge to urinate, carbachol medication and catheterization of the urinary bladder. Sex and age had no influence on the incidence. A history of disturbances of micturition increased their frequency. DISCUSSION AND CONCLUSIONS. Disturbances of micturition are the most common side effect of spinal anaesthesia during the first 24 h after surgery. Their higher frequency following the longer acting bupivacaine may be evidence of longer lasting blockade of the efferent sacral parasympathetic fibers innervating the detrusor vesicae muscle, leading to inhibition of bladder voiding. The consequences of these disturbances, if not correctly managed, may be distension of the urinary bladder with ensuing infection and loss of tone of the detrusor muscle. Various measures are recommended: choice of the longer acting local anaesthetic only if necessary, careful control of bladder filling, restrictive infusion of fluids, early mobilization, carbachol, catheterization in good time, prophylactic placement of an indwelling catheter in patients with previous disturbances.

[Cardiovascular polymorbidity as a function of psycho-organic status. A series of 904 pathological and neuropathological comparisons]. / Polymorbidité cardiovasculaire en fonction de l'état psycho-organique. Série de 904 confrontations pathologiques et neuropathologiques.

In the past decades, the recognition of polymorbidity as an important characteristic of geriatric medicine lead to important improvements in the multidisciplinary approach of the elderly. Coexistence of somatic and psychiatric diseases with various forms of etiopathogenic relations has been described early in this century. Dementia may be caused, aggravated, revealed or randomly accompanied by somatic diseases and inversely. However, very few attempts have been made in order to analyze the significance of these associations. This study is meant to give a better epidemiological knowledge of the relation between cardiovascular diseases and cerebral aging. This could lead to a better diagnostic approach and to a more complete physiopathological conception of dementia. 904 autopsy reports (patients who died between 1972 and 1986 in the Hôpital de Gériatrie of Genova) have been reviewed and classified in three groups according to neuropathological findings: 335 subjects with vascular encephalopathy of various types, 382 patients with degenerative diseases of Alzheimer type and 187 patients with normal brain. The subjects of these three groups had not all been considered demented. For each patient, age, sex, cause of death and 14 cardiovascular items have been appointed. The patients of the Alzheimer group died older and were more often women than those of the two other groups. The subjects of the vascular group died older than those of the normal group and were more often men than those of the two other groups. Stoke was considered to be the cause of death in 3% of the vascular patients whereas, by definition, it was absent from the two other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Health survey in the elderly using home interviews: study of various indicators]. / Enquête de santé chez les personnes âgées par interview à domicile: etude de quelques indicateurs.

Questions asked on the occasion of health survey at home usually refer to frequency of medical consultations and prescribed drugs, but often also to reported somatic symptoms and self-evaluated general health status. Interview data collected in a population of aged widows and widowers revealed a high degree of concordance between these various health indicators, justifying in particular the value assigned to the subjective appreciation of the level of general health.

Human monkeypox: confusion with chickenpox.

Human monkeypox is a zoonosis occurring sporadically in the tropical rain forest of western and central Africa. The exact incidence and geographical distribution are unknown, since many cases are not recognized. Special surveillance was established in three regions in Zaire in 1981 that led to a substantial increase in reported cases. The question arose as to the possibility that clinical diagnostic errors cause some cases of monkeypox to be misdiagnosed as other eruptive diseases. This paper presents the results of a study assessing the extent of and reasons for these clinical diagnostic errors in areas where health staff as well as the general public are aware of human monkeypox. In Zaire in the period 1981-1986, 977 persons with skin eruption not clinically diagnosed as human monkeypox were laboratory tested. 3.3% of human monkeypox cases were found among 730 patients diagnosed as cases of chickenpox, 7.3% among cases diagnosed as "atypical chickenpox" and 6.1% among cases with skin rash for which clinical diagnosis could not be established. The diagnostic difficulties were mainly based on clinical features characteristic of chickenpox: regional pleomorphism (in 46% of misdiagnosed cases), indefinite body-distribution of skin eruptions (49%), and centripetal distribution of skin lesions (17%). Lymph-node enlargement was observed in 76% of misdiagnosed patients. In the absence of smallpox, the main clinical diagnostic problem is the differentiation of human monkeypox from chickenpox. The presence of lymphadenopathy, pre-eruptive fever and slower maturation of skin lesions are the most important clinical signs supporting correct diagnosis of monkeypox.

The transmission potential of monkeypox virus in human populations.

Data on monkeypox in Zaire over the five years 1980-1984 are analysed to assess the protection imparted by past smallpox vaccination and the transmission potential of the virus in unvaccinated communities. Attack rates in individuals with and without vaccination scars indicated that smallpox vaccination (discontinued in 1980) imparted approximately 85% protection against monkeypox. It is predicted that monkeypox virus will continue to be introduced into human communities from animal sources, and that the average magnitude and duration of monkeypox epidemics will increase as vaccine-derived protection declines in the population. On the other hand, current evidence indicates that the virus is appreciably less transmissible than was smallpox, and that it will not persist in human communities, even in the total absence of vaccination. The findings thus support the recommendation of the Global Commission for the Certification of Smallpox Eradication to cease routine smallpox vaccination in monkeypox endemic areas, but to encourage continued epidemiological surveillance.

Human monkeypox: disease pattern, incidence and attack rates in a rural area of northern Zaire.

Human monkeypox is a zoonosis that occurs sporadically in the tropical rainforest of western and central Africa. This article presents the results of epidemiological features of 91 monkeypox patients reported in Bumba zone in northern Zaire during the period 1981 to 1985. Their age ranged from 7 months to 29 years (93% below 15 years of age). 11% of patients had visible smallpox vaccination scars. Deaths occurred sporadically; the overall case-fatality rate was 9%. 91 patients arose in 61 separate outbreaks; 42 of them consisted of only a single case. The source of infection was suspected to be animal for 70 cases, and human for the remaining 21 cases. The illness occurred in all months of the year. There was a considerable clustering of cases in the northern part of the zone. The average annual incidence rate in the observed zone was 0.63 cases per 10,000 population with marked differences in age, time and place. The average annual primary attack rate among unvaccinated individuals (1.7/10,000) sharply contrasted with those vaccinated (0.04/10,000). The secondary attack rate for contacts without vaccination scar (4.3%) differed significantly from those who had been vaccinated in past (0.7%). Many unvaccinated contacts living under conditions of maximal exposure to index cases escaped not only the disease but also infection. The low incidence rate of human monkeypox indicates its limited public health importance even in a well-known enzootic area.

High density lipoprotein (HDL) subfractions in cardiovascular patients with low levels of HDL-cholesterol. Influence of hypertriglyceridaemia on subfraction concentration and composition.

The major high density lipoprotein (HDL) subfractions were examined in angiographically defined cardiovascular patients with low HDL-cholesterol (HDL-C) levels. The aims were to study subfraction concentration and composition, and the extent to which hypertriglyceridaemia (HTG) modified these variables. Normotriglyceridaemic (NTG)-low HDL-C patients showed similar subfraction composition to age-matched healthy controls. However, these groups showed notable differences in subfraction composition compared to HTG-low HDL-C patients, particularly with regard to the HDL2 subfraction. HDL subfraction mass was significantly reduced in both cardiovascular groups; the HTG group showed a greater reduction in HDL2, whilst the NTG group showed a greater reduction in HDL3. The major HDL apoprotein (apo A-I) was lower in both subfractions of the cardiovascular patients. Apo A-II showed significant reductions only in the HTG patients.

Clinico-epidemiological features of monkeypox patients with an animal or human source of infection.

Clinical and laboratory examinations were carried out on a total of 338 monkeypox patients in Zaire from 1981 to 1986. An animal source of infection was suspected in 245 (72%) and interhuman transmission for the remaining 93 patients. Among those whose infection was presumably acquired from an animal source, the most affected groups were children aged 3-4 years (27%) and 5-6 years (20%), while only 4% of cases were over 15 years old; there was a considerable preponderance of males (58%) over females (42%), especially in the age group 5-14 years. Among those presumably infected by person-to-person transmission, the age distribution was more uniform, adult patients tending to be relatively more common, and there were more females (57%) than males (43%).Based on comparisons of the frequency and intensity of clinical signs and symptoms among patients infected from an animal source and those who were infected by another patient, there was no evidence that the disease becomes more severe and the transmitted virus more virulent or more easily transmissible from person to person after one or more passages through human hosts.

Human monkeypox: secondary attack rates.

Data on human monkeypox collected in Zaire during the six years 1981-86 were analysed to assess the extent of interhuman transmission of monkeypox virus. Among the 2278 persons who had close contact with 245 monkeypox patients infected from an animal source, 93 fell ill and were presumed to have been infected from the known human source: 69 of these were spread in the first generation, 19 in the second generation, and the remaining five cases in the third and fourth generation.The secondary attack rates were correlated with the age, sex, place of residence, and vaccination status of the contacts. There was an overall 3% probability of becoming ill following infection from a known human source. The affected household was the main focal point for interhuman transmission of monkeypox virus. The highest attack rate (11.7%) occurred among unvaccinated household contacts in the age group 0-4 years. However, the majority of susceptible persons who had been close to patients in the confined space of poorly ventilated huts failed to develop illness. There was no evidence of an increase in the secondary attack rate between 1970-80 and 1981-86.The inefficient spread from person to person, even in conditions of maximum exposure, supports the concept that monkeypox virus is poorly adapted for sustained transmission between humans and that such transmission does not pose a significant health problem.