A randomized trial to study the effect of automatic cluster remover settings on milking performance, teat condition, and udder health.

The objectives were to study the effect of 2 different automatic cluster remover settings on (1) milking characteristics, (2) milk component yields, (3) teat tissue condition, and (4) udder health. In a randomized controlled field trial, Holstein cows (n = 689) from 1 commercial dairy farm with a thrice-daily milking schedule were allocated to 2 treatment groups. Treatment consisted of a cluster remover take-off milk flow threshold of 1.2 (ACR1.2) or 0.8 kg/min (ACR0.8) for 57 d. Milking characteristics (milk yield; and milking unit-on time, MUOT) were obtained with electronic on-farm milk meters. Composite milk samples were collected and analyzed for fat, protein, lactose, and somatic cell count. Machine-milking-induced short- and long-term changes to the teat tissue condition were assessed visually. General linear mixed models demonstrated differences in MUOT, whereas no meaningful differences in milk yield were detected. Milk yield (least squares means, 95% confidence interval) was 11.3 (10.9-11.8) and 11.3 (10.8-11.8) kg in groups ACR1.2 and ACR0.8, respectively. The effect of treatment on MUOT was modified by parity. Milking unit-on time in first-, second-, and ≥third-lactation cows, respectively, was 260.7 (252.0-269.4), 257.8 (247.4-268.1), and 260.2 (252.6-267.9) s in group ACR1.2; and 273.7 (264.9-282.5), 279.1 (269.4-288.8), and 295.7 (287.9-303.6) s in group ACR0.8. We detected no meaningful differences in milk component yields or linear somatic cell score. Least squares means in groups ACR1.2 and ACR0.8, respectively, were milk fat yield, 0.42 (0.40-0.44) and 0.42 (0.40-0.44) kg; milk protein yield, 0.36 (0.35-0.37) and 0.37 (0.36-0.37) kg; milk lactose yield, 0.61 (0.60-0.63) and 0.63 (0.61-0.64) kg, and linear somatic cell score, 1.9 (1.8-2.0) and 1.9 (1.8-2.0). A generalized linear mixed model revealed an effect of treatment on machine-milking-induced short-term changes. The odds of short-term changes to the teat tissue were lower for cows in group ACR1.2 [odds ratio (95% confidence interval) = 0.78 (0.63-0.96)]. No meaningful differences were detected in machine-milking-induced long-term changes between treatment groups. Increasing cluster remover take-off milk flow threshold from 0.8 to 1.2 kg/min decreased individual milking duration and alleviated machine-milking-induced short-term changes to the teat tissue without adversely affecting milking performance or somatic cell count. Future studies are warranted to investigate the effect on milk production and udder health over a whole lactation period.

The value of glycosylated hemoglobin (HbA1c) as a predictive risk factor in the diagnosis of diabetes mellitus (DM) in the elderly.

In order to evaluate the significance of HbA1c in the diagnosis of Diabetes Mellitus (DM) and the risk of future DM in the elderly, the HbA1c and the fasting glycemia of 2167 elderly subjects of 65-84 years were determined, taking part in the epidemiological Italian Longitudinal Study on Aging (ILSA). The subjects were divided in 3 groups according to their glycemic values, namely those with normal fasting glucose (NFG), with impaired fasting glucose (IFG), and diabetics. It has been revealed that the values of HbA1c in these 3 groups overlapped in more than 80%. The evaluation of the HbA1c levels represents a clearly lower diagnostic validity for the DM, than the fasting plasma glucose (FPG). The identification of new cases of DM in a follow-up of 3 years was modest: in the NFG group (2.35% among those who had an HbA1c<7.02 and of 2.99% of those who had HbA1c>7.02%), while in the IFG group the same analysis gave 14.14% of those with normal HbA1c, increasing progressively in parallel with the increase of the HbA1c values above 7.02%, reaching 19.59%. It is evident from these results, in agreement with the multifactorial characteristics of type 2 DM that one has to look for other predictive factors, such as the dysmetabolic lipid components, and first of all the genetic ones in the predictive diagnosis of DM.

Pharmacotherapy in the extreme longevity.

The increased longevity brings to the appearance of more polypathologies, being frequently of chronic-degenerative type, and also an increased use of pharmaca. The present study evaluated the usual drug consumption in the ultralongevous people in comparison with their clinical conditions. A total of 602 centenarians were involved: clinical anamnesis, objective examinations and clinico-functional evaluations were performed. In 555 of them an acceptable pharmacological anamnesis was obtained. The results showed that 28 centenarians (5%) did not take any drug, 527 (95%) of them used regularly some pharmacological therapy. Their distribution was: 1 drug/day 68 (13%), 2 drugs/day 86 (16.3%), 3 drugs/day 344 (65.2%), more than 3 drugs/day 29 (5.5%). The mean daily drug consumption was 2.7+/-1.4. Good clinical conditions could be established in 115 (20.7%) of the centenarians, of them 28 subjects (24.3%) had used no drugs, 87 (75.7%) of them used 1-3 drugs/day. It was an important observation that adverse drug events (ADE) occurred in 15.2%. The ADE occurs frequently also in polypharmacological treatments, with various pharmacodynamic and pharmaco-kinetic modifications of the drugs. The mean daily drug consumption of the ultralongevous subjects was lower than that of the common elderly. This may be due to the past life of our centenarians, characterized by satisfactory health conditions, and also to a higher attention of the general practitioners in the drug prescriptions, as well as of the family members who administer the pharmaca.

Cognitive and functional status in the extreme longevity.

Usually, the effects of cognitive decline are not noted before the age of 70 years, which involve the intellectual capacities, the attention, the processes of elaboration and the memory. The studies on the cognitive disturbances of the elderly are numerous, and document the progressive increase of cerebral deterioration with advancing age. However, only a few studies refer to the significance of the cognitive disturbances in the clinical conditions and autonomy of the long living subjects. For this reason, we studied the cerebral deterioration of an adequate number of centenarians in correlation with their clinical conditions and autonomy. Our centenarian sample derived from the Italian multi-center study on centenarians (IMUSCE), which was an epidemiological study which identified 1173 centenarians (202 males, 971 females) in the age range of 100-109 years. From this sample, we analyzed 346 subjects as far as the cognitive functions and the degree of autonomy by using the psychometric tests of the mini-mental state examination (MMSE) and the instrumental activities of daily living (IADL) for the functional evaluations. In addition, we evaluated the clinical conditions of the subjects dividing them in three groups: Group A (those in good clinical conditions), Group B (those in discrete clinical conditions), and Group C (those in deteriorated clinical conditions). These analyses revealed that 187 (54.1%) of the 346 examined centenarians have shown an MMSE score in the normal range (score ratio from 1.0 to 0.63). The cognitive disorders are present in the centenarians in a clearly higher frequency (13.1%), than found in the common elderly (5.1%). The severe cognitive disorders do not allow a total autonomy or even a slight dependency. Only six subjects (1.7%) of the total sample were totally independent. These subjects had no cognitive disorders, and were in good clinical conditions. The results show that having an MMSE score in the normal range, and being in good clinical conditions are necessary but not sufficient prerequisites for a total autonomy in the IADL scores.

Diabetes mellitus in the extreme longevity.

Epidemiological studies have revealed a progressive increase in the prevalence of diabetes mellitus in the elderly. Numerous factors are responsible for this trend, among them there are (a) the long-lasting disease due the improved therapeutic remedial (pharmacological, dietary treatments and physical activity), (b) the increased life span expectancy. The prevalence of diabetes mellitus in long living subjects is lower than in elderly people (subjects aged from 65 to 84). Senile diabetes is prevalent in long living people, and usually begins after 90 years. The incidence of neodiagnosed diabetes is higher in the oldest old than in the elderly people. Based on the results, diabetes mellitus is a negative factor for survival, and does not usually allow to achieve very old age, i.e. centenarian.

Laboratory parameters in centenarians of Italian ancestry.

Studies aimed at collecting reference parameters for haematochemical analysis in the elderly are scarce and for the oldest old subjects even more rare. In order to establish the reference values for the most common laboratory text in long living individuals, we measured haematochemical parameters in >100 years old subjects and in aged subjects as control. Six hundred and two centenarians accepted to be enrolled in the study. A case history containing the complete anamnesis, clinical examinations, evaluation of the clinical cognitive and functional tests, was prepared for each centenarian. Blood samples from 120>100 years old subjects free of chronic or acute Illness (i.e. Alzheimer's disease, metabolic diseases, cardiovascular disease, stroke, neoplastic and infectious diseases) were analysed. A population of 381 healthy old subjects (age range 65-85 years old), recruited in the same geographic areas and with the same clinical characteristic of the health centenarians, was utilized as control. Significant differences were observed for blood glucose, ALT, cholesterol and platelet levels, reduced in centenarians respect to the old subjects, whereas blood urea nitrogen levels were found significantly increased in centenarians. In conclusion, reference values of the healthy adults can generally been utilized also for the healthy oldest old group, with the notable exception of the above mentioned laboratory parameters that appear to be modified in long living subjects.

Genealogy of centenarians and their relatives: a study of 12 families.

The longevity is a complex phenomenon in which specific genetic properties seem to play a role. The present study intended to reconstruct the genealogical tree of 12 subjects, being residents of one Northern and one Southern province of Italy, in order to establish the longevity of the ancestors. Detailed studies have been performed in the registry offices and the historic archives. The research method started from the identification of the centenarians on the basis of the documentation of the relevant birth document, it was continued by identifying the documents of birth, marriages and death of the parents of the centenarians. This way we proceeded systematically backwards in time. In addition, we verified the medium life span of the Italian population in the given periods of time, when the centenarians and their ascending lines had lived. These results offer clear historic-statistical evidences for the genetic basis of longevity.

Diabetes mellitus in the elderly: diagnostic features.

The new diagnostic criteria of the diabetes do not consider the age of the subjects. It has been demonstrated that the fasting glucose values as well as the glycemia levels after oral glucose load increase with age. Therefore, it is necessary to evaluate whether the new diagnostic criteria are valid for the elderly subjects also. In spite of the findings that among the subjects with fasting glycemia of 126-140 mg/ml subsequent controls after long times often revealed the presence of impaired fasting glucose (IFG) and numerous cases with IFG displayed values <110 mg/dl after longer times, the present authors accept the new diagnostic criteria even for the elderly subjects. However, they emphasize the importance of distinguishing diabetes in the elderly in subclasses, such as clinically manifest diabetes, mild diabetes and diabetic glucose tolerance (DGT) type, in order to establish the early diagnosis of diabetes, and therefore, to prevent the chronic vascular complications.

Successful aging in centenarians: myths and reality.

The term "successful aging" appeared in the first issue of "The Gerontologist" in 1961. During the successive years, this expression has changed its meaning. Nowadays, successful aging means "absence of diseases and disabilities, maintenance of high levels of physical and cognitive abilities, preservation of the social and productive activities". It has become a common opinion that the centenarians may represent the prototypes of the successful aging. This motivated our work to study the clinical, psychical, and functional aspects in a centenarian group, verifying the real autonomy, instrumental capacities, and working abilities. Our study pool consisted of 602 centenarians, who were also subjects of then epidemiological studies of the Italian Multicenter Studies on Centenarians (IMUSCE). All subjects underwent a clinical-anamnestic evaluation, cognitive-functional tests by means of the mini mental state examination (MMSE), the independence index in activities of daily living (ADL), the instrumental activities of daily living (IADL) scale. The centenarians were classified in three groups, according to the criteria elaborated previously by us, based on their psychophysical status and autonomy, as follows. Group A: centenarians in good health status; Group B: centenarians in an intermediate health status. Group C: centenarians in bad health status. Group A represented 20.0% of the total pool, Group B amounted to 33.4%, and the Group C was 46.6%. The centenarians of Group A presented normal ADL values, and 47.9% of them were autosufficient in all functions; 5.7% of them were independent in all IADL items. These data confirm that the centenarians of Group A are free of invalidating chronic diseases, are autonomous, maintain good physical and cognitive capacities, however, have not maintained any social or productive activities. Therefore, they cannot be considered as prototypes of successful aging.

Alterations of the lymphocytic set-up in elderly patients with cancer.

It is assumed that the increased incidence of neoplastic pathologies with advancing age is correlated with the immunosenescence and with the altered immune-surveillance. The present study was aimed at evaluating the role of the immunocompetent system and immunosenescence in carcinogenesis. A pool of 99 subjects (38 females, 61 males) has been analyzed in three groups as follows. Group A: 51 elderly subjects with cancer (16 females and 35 males, average age 73.7 +/- 7.5 years). Group B: 24 young subjects with cancer (12 females, 12 males, average age 49.5 +/- 10.3 years). Group C: 24 elderly subjects without any clinical evidence of cancer (10 females, 14 males, average age 74.6 +/- 6.3 years). Hemo-chromocytometric analysis and cytofluorimetric typifying have been performed in all subjects. A decrease of T (CD3+)-lymphocytes has been observed in group A, if compared to group B (P < 0.007), and to group C (P < 0.01), The T (CD4+)-lymphocytes were fewer in group A, than in group C (P < 0.004), and also the NK cells showed the same trend (P < 0.002). The numbers of leukocytes and monocytes increased in group A compared to group C (P < 0.01 and P < 0.004, respectively). Red cell numbers, hemoglobin and hematocrit values were lower in group A than in group B (P < 0.03, P < 0.03, P < 0.01, respectively), and also than in group C (P < 0.007, P < 0.001, P < 0.01, respectively), The results demonstrate that the alterations of the immunocompetent cells, particularly of the T-cell pool, may play an important role in the carcinogenesis of the elderly.

Use of interleukin-2 in advanced renal carcinoma: meta-analysis and review of the literature.

OBJECTIVE: Interleukin-2 (IL-2) is a glycoprotein that influences the immunoendocrine network by several actions. This cytokine is commonly used in the patients with renal carcinoma, both as neo-adjuvant treatment prior to surgery and as adjuvant therapy. The aims of our study were to evaluate the IL-2 efficacy on postoperative survival rate in patients with metastatic renal carcinoma, to compare the efficacy of treatment with IL-2 alone with the results achieved by conventional systemic chemotherapy or association protocols IL-2-based and to examine the toxic effects of the IL-2-based therapeutic regimens in renal cell carcinoma (RCC). DESIGN: We enrolled 7 randomised trials concerning the IL-2-based treatments of RCC and performed meta-analytic processing by the Mantel-Haenszel-Peto method in order to achieve odds ratios and 95% confidence intervals of the examined treatments. We also considered 11 non-randomised trials, evaluating them in terms of survival rate through the endpoints available. In all trials taken into account, we finally examined the toxic effects as WHO grade, specifying study by study the main site involved. RESULTS AND CONCLUSIONS: Complete or partial response rates have been obtained in 6% to 30% of treated patients in all the trials considered. Our study revealed the need for careful screening as well as a continuous adjustment of doses when an immunotherapeutic protocol is employed in order to treat a metastatic renal carcinoma. Treatment with IL-2 alone achieves better results than systemic chemotherapy, even if the two types of treatment showed an almost overlapping medium- to long-term mortality rate. IL-2 plus lymphokine-activated killer cells accomplish only a partial response. The protocol with IL-2 plus IFN alpha displayed an interesting efficacy associated with a low toxicity even if the cumulative toxic effect of the two drugs should be carefully monitored. To date, the association of tumour-infiltrating lymphocytes, IL-2 and IFN alpha provided the best results in terms of survival and toxicity.

Immunosenescence and cancer: a review.

The human neoplastic pathologies are age-dependent. The increased occurrence of tumors observed with advancing age may be determined by the accumulation of certain phenomena promoting different phases of neoplastic processes. In these events, important roles can be attributed to mutations of the genome that accumulate during aging and to the immunosenescence. It may be hypothesized that certain tumors controlled by the immune system may become more frequent in the elderly as a consequence of the decreased functionality of this important defense system of the organism. Nevertheless, the problems of the interrelationships between the immunosenescence and tumors are seriously contradictory. Therefore, on the one hand, one has to establish how much the immunodeficit of the elderly patient may be responsible for the neoplastic pathology, while on the other hand, one cannot neglect important environmental and pathophysiological factors in these cases.

Immunosenescence: a review.

Aging involves the morphological and functional integrity of all organs, including the cellular and humoral immunological functions. The main alterations can be listed as follows: (i) Thymic involution resulting in the decreased number of lymphoid precursor T- and B-cells. (ii) Reduced proliferative capacity of T-cells; loss of lymphocyte subgroups as a consequence of the shortening of telomeres. (iii) Qualitative deficiency of B-lymphocytes with a reduced response to exogenous antigens. (iv) Compromised activity of the accessory cells, both directly by depressing the chemotactic and phagocytic responses, and indirectly by increasing the prostaglandin production which inhibit the proliferation of T-cells. (v) Alterations in the production and secretion of various cytokines. (vi) Other factors like the general physiological conditions, the nutritional state, psychological habit and various hormone levels.

Antiviral drugs in chronic hepatitis B: review and meta-analysis.

Many researchers have attempted to identify the drugs capable of acting on the viral replication cycle and maintaining clinical remission in chronic hepatitis B. We evaluated the efficacy of antiviral drugs in chronic hepatitis B, by examination of 20 controlled and non-controlled trials conducted between 1985 and 1996. In chronic hepatitis B, adenine arabinoside and its monophosphate did not achieve satisfactory results, even though combination therapy with cortisone seemed to achieve very good results (remission rates ranging from 45% to 66% in patients treated). Lamivudine did not seem to furnish lasting effects in chronic hepatitis B, because many patients relapse after suspension of the treatment due to the appearance of HBV variants resistant to the drug. Contrasting results were observed with famciclovir. Treatment of chronic hepatitis B, with this drug seemed capable of reducing HBV-DNA serum levels by a mean of 50% compared to pretreatment values, with normal alanine aminotransferase levels in about 30% of treated patients. Ganciclovir treatment of chronic hepatitis B seemed to furnish good, but transient, results. Even if no antiviral drug represented a valid alternative to interferon, antivirals may become the drugs of choice in chronic hepatitis B, because they are aimed at the etiology of disease.

Increase of serum beta2-microglobulin in patients affected by HCV correlated hepatocellular carcinoma.

OBJECTIVE: HLA antigens influence tumour growth and spreading, but the mechanism is still unclear. Increased serum levels of beta2-microglobulin (beta2MG) have been found in several chronic inflammatory and tumour diseases. The aim of the present study was to analyse the relationship between serum beta2MG levels and some markers of tumour progression, to verify the reliability of this parameter as a marker of hepatocellular carcinoma (HCC) progression. DESIGN: We studied 50 patients with hepatitis C virus (HCV) correlated HCC, 50 patients affected by chronic hepatitis C and 20 healthy controls. We performed a statistical analysis on the data obtained from haematological withdrawals in patients and healthy subjects. METHODS: Serum beta2MG levels were determined by an immunoturbidimetric method (normal values range from 0.8 to 27 microg/ml). Diagnosis of HCC was performed on the basis of haematochemical parameters (alpha-fetoprotein) and instrumental examinations (ultrasonography and computed tomography). In order to perform the statistical analysis we used the Wilcoxon non-parametric rank test and the Spearman log-rank correlation test RESULTS: Patients with HCC showed higher serum beta2MG levels than did chronic hepatitis C patients (36+/-16.5 microg/ ml versus 2.3+/-0.8 microg/ml; P<0.0001) or healthy subjects (36+/-16.5 microg/ml versus 1.6+/-0.4 microg/ml; P<0.0001). We found a positive correlation between beta2MG and interleukin-6 (IL-6) (r = +0.3; P = 0.05), beta2MG and alpha-fetoprotein (r = +0.4; P = 0.005), beta2MG and tumour size (r = +0.3; P = 0.02). CONCLUSIONS: An increase in the beta2MG serum level reflects the tumour size and seems to be a consequence of the stimulation on hepatocytes by humoral components of immunological response, such as IL-6. Weakening of the immune system, due to IL-6, may be responsible for a more severe progression of HCC and the hyperexpression of beta2MG.

Serum carnitine levels in chronic hepatitis C patients before and after lymphoblastoid interferon-alpha treatment.

OBJECTIVE: Chronic liver disease is often a hypocarnitinaemic condition. Since carnitine affects lipid metabolism, modifications of lipid pattern and energy metabolism can be expected in patients affected by chronic viral hepatitis. The aim of this study was to assess the relationship between serum carnitine levels and the grading of chronic hepatitis C, and to evaluate the effects of lymphoblastoid interferon (IFN)-alphan1 on carnitine levels in patients with hepatitis C. DESIGN: We evaluated carnitine serum levels in a group of 32 patients with chronic hepatitis C before and after treatment with intramuscular IFNalpha 3MU 3 times/week for 6 months, comparing them with levels in 20 healthy controls. Statistical correlations between serum carnitine, histological activity index score, duration of disease and lipid pattern were also evaluated. RESULTS: Serum carnitine levels, which were statistically lower in hepatitis C patients than in controls before therapy, increased after IFNalpha (p = 0.0003 vs pretreatment). There were no significant changes in total cholesterol in any patient after treatment, although serum triglyceride levels increased (p = 0.0003). Serum carnitine levels were correlated with age (r = 0.35; p = 0.02), type of response (r = - 03; p = 0.04), duration of disease (r = - 0.8; p = 0.0001) and high-density lipoprotein cholesterol levels (r = 0.43; p = 0.005) after completion of IFNalpha treatment. CONCLUSION: It is suggested that the post-treatment increase in serum carnitine observed in this study could be considered a new index of improved liver function. Also, exogenous administration of carnitine may be useful in patients with chronic hepatitis C who have reduced endogenous synthesis of this substance.

Interferon alpha-induced depression in chronic hepatitis C patients: comparison between different types of interferon alpha.

IFN alpha treatment is able to produce dose-related side effects, such as depression, in the central nervous system. We assessed the effects on depression of four different types of IFN alpha (recombinant IFN alpha 2a, recombinant IFN alpha 2b, lymphoblastoid IFN alpha, leukocyte IFN alpha), administered at the same doses in four homogeneous groups of chronic hepatitis C patients (96 patients; 24 patients for each group). A group of 18 untreated hepatitis C patients was considered as a control group. Depression was measured using Zung's self-rating depression scale (SDS scale) before starting IFN alpha therapy and at the 1st, 3rd and 6th month of treatment. In all patients evaluated, mean SDS values increased from mild to moderate depression, but never attained severe depression (SDS > 70). More elevated SDS values were observed in the 1st month of treatment, with a progressive decrease during the end points above-mentioned. The recombinant IFN alpha 2a and lymphoblastoid IFN alpha arms presented higher SDS mean scores compared to the recombinant IFN alpha 2b and leukocyte IFN alpha arm. Only in the leukocyte IFN alpha arm SDS values returned to basal values at the 6-month end point. Leukocyte IFN alpha seemed to present a more elevated tolerability than other IFN alpha types available for clinical practice. A very careful selection of hepatitis C patients is required before starting IFN alpha therapy.

Serum interleukin 6 concentrations in chronic hepatitis C patients before and after interferon-alpha treatment.

IFN-alpha represents the treatment of choice in chronic hepatitis C. It acts directly on the cells infected by the virus and indirectly via the cytokine network. We studied the behavior of interleukin 6 (IL-6), a cytokine that is particularly active in the liver and considered an index of liver inflammation and necrosis, in order to evaluate the relationships between IFN-alpha administration and serum levels of this cytokine. Our study series was composed of 60 patients (32 males, 28 females, mean age 53.03 +/- 12.7 years) affected by chronic hepatitis C and 24 healthy controls (14 males, 13 females, mean age 45.8 +/- 5.9 years). We determined serum IL-6 concentrations before and after 3,000,000 IU of IFN-alpha t.i.w./6 months in the former and compared them with levels observed in the controls. Pre- and post-treatment serum IL-6 levels were higher in chronic hepatitis patients and correlated with HAI score and HCV RNA prior to treatment. Diversely, this correlation was less significant after completion of the treatment. Furthermore, IL-6 concentrations depended on the type of response to treatment, i.e. they decreased in complete responders, while increased in partial and non-responders. Our data indicate that IL-6 concentrations, before treatment, are expression of viral-induced inflammation and that, after treatment, may be increased by the action of IFN-alpha treatment.