Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers.

The study was performed to evaluate the relative sensitivity of various noninvasive methods to detect and describe the systolic cardiovascular effects of stepwise increasing doses of isoproterenol: two-dimensional left ventricular echocardiography (main variable, ejection fraction), ACVF (attenuation compensated volume flow)--dual-beam Doppler echoaortography (time-averaged mean velocity), electrical impedance cardiography [(dZ/dtmax)/RZ index], and systolic time intervals from mechanocardiography (PEP and QS2c). Isoproterenol was administered by constant rate intravenous infusion in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 minutes). Saline control infusions were given in analog fashion. The treatments (isoproterenol and saline solution) were administered in a period-balanced two-way crossover design with randomly allocated sequences. The subjects, observers, and analysts were blinded to the treatment protocol. Study subjects were 10 healthy male volunteers (age range, 23 to 31 years; mean age, 26.6 years). Compared with saline solution, isoproterenol caused a dose-related increase in ejection fraction, (dz/dt)/RZ index, and time-averaged mean velocity and a dose-related shortening of PEP and QS2c. The responses are congruent with an enhancement of cardiac systolic performance caused by a positive inotropic stimulation and an afterload reduction ("inodilatory" response). The effects on systolic time intervals reached statistical significance (alpha = 0.05) at the first isoproterenol dose step, the effects on the impedance cardiography and the Doppler echoaortography variables reached statistical significance at the second dose step, and the effects on the two-dimensional echocardiography reached statistical significance at the third dose step. All methods allowed to detect isoproterenol-related changes. Systolic time intervals were the most sensitive, followed by impedance cardiography, ACVF--dual-beam Doppler echoaortography, and two-dimensional echocardiography. The practical convenience and high sensitivity of the systolic time intervals makes them suitable to evaluate investigational systolic inodilatory changes in humans.


Effects of bezafibrate on insulin sensitivity and glucose tolerance in subjects with combined hyperlipidemia.

To investigate whether the lowering of triglyceride levels has beneficial effects on glucose metabolism, we studied 13 nondiabetic men with combined hyperlipidemia (phenotype IIB) before and after 2 months of treatment with a slow-release formulation of bezafibrate (400 mg daily). The rates of whole body glucose disposal were quantitated by the euglycemic hyperinsulinemic clamp technique (insulin infusion rate of 80 mU/m2/min). In an oral glucose tolerance test, fasting glucose level decreased slightly (5.0 +/- 0.2 versus 4.8 +/- 0.2 mmol/L; p < 0.05) during bezafibrate treatment. Glucose and insulin levels after an oral glucose load remained unchanged. Rates of whole body glucose disposal did not change during bezafibrate treatment (39.5 +/- 3.3 mumol/kg/min before treatment versus 40.6 +/- 2.7 mumol/kg/min after treatment; difference not significant). Basal hepatic glucose output also remained unchanged (8.2 +/- 0.2 mumol/kg/min before treatment versus 8.3 +/- 0.2 mumol/kg/min after treatment; difference not significant). Our findings show that bezafibrate has a triglyceride-lowering effect without any significant influence on insulin sensitivity.


Nasal spray nicotine replacement suppresses cigarette smoking desire and behavior.

The effects of short-term nasal spray nicotine replacement in suppressing desire to smoke and ad libitum cigarette smoking behavior were evaluated in male and female smokers. In study I, 10 male and 10 female smokers received intermittent doses of 0, 7.5, 15, and 30 micrograms/kg nicotine by way of measured-dose nasal spray, with each dose on a separate day. Self-reported desire to smoke was significantly suppressed by each nicotine dose compared with placebo, but there were no significant differences among nicotine doses or between men and women. In study II, eight male and eight female smokers received 0, 15, and 30 micrograms/kg nicotine intermittently and were allowed to smoke their preferred brands of cigarettes ad libitum. Similar to study I, nicotine replacement significantly suppressed number of cigarettes smoked, number of puffs, and carbon monoxide boost and increased latency to smoking, but there were almost no significant differences between the two nicotine doses. Magnitude of smoking suppression attributable to 15 micrograms/kg tended to be greater in men than in women. However, plasma nicotine concentrations were significantly higher after 15 and 30 micrograms/kg versus placebo, suggesting only partial compensation in smoking behavior with short-term nasal nicotine replacement. These findings support the idea that short-term nicotine replacement decreases smoking desire and behavior, but the findings indicate that smoking behavior is partly influenced by factors other than nicotine regulation.


Racial and gender differences in N-acetyltransferase, xanthine oxidase, and CYP1A2 activities.

The urinary molar concentration ratios of several caffeine metabolites are indicators of specific drug metabolizing enzyme activities. The ratios of 5-acetyl-amino-6-formylamino-3-methyluracil (AFMU) to 1-methylxanthine (1X), AFMU to 1X plus 1-methyluric acid (1U), and AFMU to 1X + 1U + AFMU are indicative of N-acetyltransferase (NAT) activity; the ratios of 1U to 1X and 1U to 1U + 1X indicate xanthine oxidase activity; and the ratio of the sum of 7-demethylated metabolites (AFMU + 1X + 1U) to the precursor for all three compounds, paraxanthine (PX), is a putative indicator of CYP1A2 oxidative activity. Our objective was to discern whether there are race-, gender-, and age-related differences in these indexes of drug-metabolizing activity. In 342 normal healthy unrelated subjects, metabolites were measured in urine collected after administration of low-dose caffeine. By two-way analysis of variance, NAT activity was higher in black subjects than in white subjects when assessed as AFMU/(1U + 1X) or as AFMU/(AFMU + 1U + 1X) (p = 0.001 and p = 0.002, respectively), but less so by use of AFMU/1X (p = 0.08). Xanthine oxidase activity, as assessed by 1U/1X or as 1U/(1U + 1X), was lower in black subjects than in white subjects (p = 0.02 and p = 0.001, respectively) and was lower in males than in females (p = 0.001 for both ratios). Females had higher AFMU/1X ratios (p = 0.03) because of higher xanthine oxidase activity. In a model in which AFMU/1X was the dependent variable and race, sex, age, and an index of xanthine oxidase (1U/1X) were independent variables, only race and 1U/1X were significant determinants of this NAT index (p = 0.003 and p < 0.001, respectively). The CYP1A2 ratio was lower in black subjects (p = 0.036) and in females (p = 0.015). Racial and gender differences in xanthine oxidase activity render the AFMU/1X ratio less reliable as an assessment of NAT activity in a heterogeneous population compared with the AFMU/(1U + 1X) or AFMU/(AFMU + 1U + 1X) ratios. The observed racial and gender differences in NAT, xanthine oxidase, and CYP1A2 activities may have implications for racial and gender differences in drug effects and carcinogen biotransformation.


Activity of oxidative routes of metabolism of debrisoquin, mephenytoin, and dapsone is unrelated to the pathogenesis of vinyl chloride-induced disease.

The hypothesis, that cytochrome P4502D6, cytochrome P4502CMP, cytochrome P4503A4 or N-acetyl-transferase may form active intermediary metabolites that could be etiologically related to vinyl chloride-induced disease was investigated in 21 drug-free workers with previous development of vinyl chloride-induced disease and in 23 drug-free workers from the same plant who did not develop the syndrome. Each subject received simultaneous oral administration of debrisoquin (10 mg), mephenytoin (100 mg), and dapsone (100 mg). Measurement of the debrisoquin recovery ratio, the 8-hour recovery of 4-hydroxymephenytoin, and the dapsone recovery ratio in the subsequent 8-hour urine sample provided in vivo phenotypic indexes of cytochromes P4502D6, P4502CMP, and P4503A4 activity, respectively. An 8-hour blood sample was used to measure the acetylation ratio, a measure of N-acetyltransferase activity. The frequency distributions of each drug metabolizing activity were similar between groups. Within this small sample, there was no evidence to implicate cytochromes P4502D6, P4502CMP, and P4503A4 and N-acetyltransferase in the pathogenesis of vinyl chloride-induced disease.


Translocation (8;12)(q13;q15) in a pediatric tumour.

A reciprocal translocation, t(8;12)(q13;q15), was found to be the sole karyotypic change in a deep-seated lipogenic tumour in a 3-year-old child. Judging from recent data on the cytogenetic characterization of adipose tumours, this finding seems to support the histopathologic diagnosis of lipoma in spite of foci of atypical cells observed at the histologic examination.


Coefficients of relationship by isonymy among Scottish males with early and late onset cancers.

Studies of certain cancers suggest that early onset cases tend to have a more pronounced hereditary component than late onset cases. We have analysed data from 60,924 Scottish males with cancer of the stomach, colon, rectum, prostate or bladder, using the coefficient of relationship by isonymy to compare patients whose age at registration was below the median with those whose age at registration was equal to or above the median. There was no evidence for greater isonymy in younger patients suggesting that, although known genetically determined cancers may have earlier onset than other cancers at the same site, early age at onset is not widely associated with a familial predisposition to malignancy.


Anti-dsDNA and Sm autoantibodies in systemic lupus erythematosus.

During the present study the coincidence of anti-dsDNA and Sm antibodies was detected in 16 percent of 51 consecutive SLE patients. These antibodies were detected by the standard indirect immunofluorescence and Ouchterlony tests. All patients with anti-dsDNA and Sm antibodies showed disease activity, including renal, CNS and pulmonary disease. We excluded a cross reactivity of these antibodies by ELISA, using competitive experiments with dsDNA and Sm antigens. The results support the presence of multiple autoantibody production during SLE activity, and suggest that different mechanisms may underlie the induction and regulation of both autoantibodies.


Bacterial arthritis in a district hospital.

Between 1977 and 1988 in the Enschede hospital 72 patients were seen with bacterial arthritis of one or more joints. Staphylococcus aureus was most frequently the causative agent (52%) and the knee was the most frequently infected joint (42%); the mortality rate was 11%. Complete restoration of pre-existent function was seen in 52% of the affected joints. In patients with severe deterioration of joint function after the bacterial infection, the period between the first symptoms and start of treatment (mean 30 days) was significantly longer than in patients with no or moderately deteriorated joint function (mean 10 days). The primary focus was mostly a skin infection, predominantly localized on the lower extremities. Half of all cases of bacterial arthritis occurred in patients with rheumatoid arthritis (RA). We therefore conclude that patients with RA and skin infections, especially if localized on legs or feet, should be treated without delay and that one should not hesitate to prescribe antibiotics. Erythrocyte sedimentation rate (ESR) was less than 20 mm after one hour in 13% and blood leucocyte count less than 10 x 10(9)/liter in 55% of all patients, showing that a normal ESR and/or blood leucocyte count do not exclude bacterial arthritis. In 4 out of 9 patients with infected prosthetic joints the infection resulted in loosening of the joint, before antibiotic treatment was started. In the other 5 patients bacterial arthritis recurred, in one patient resulting in loosening of the joint, only shortly after stopping long-term successful antibiotic treatment (6-24 months). Thus, we feel that lifelong treatment with antibiotics is a reasonable alternative in cases, where the risk of surgery is very high.


IgD serum levels are influenced by HLA-DR phenotype.

In the present paper we have evaluated IgD serum levels of 84 randomly selected HLA-typed healthy Sicilians. The values were analysed according to age, sex and HLA-DR phenotypes. No correlation between age and IgD serum levels was found in our population since all subjects were in a narrow age range. Furthermore, no significant association was found between IgD serum levels and gender of studied subjects. The evaluation of IgD serum levels according to HLA-DR phenotypes revealed that HLA-DR1 positive subjects displayed significantly higher values. These results are in agreement with previous reports showing that HLA phenotypes may be involved in the control of serum immunoglobulin levels. Furthermore, present data strengthen our suggestion that HLA-DR1 phenotype is related to the 'high responder' immunological profile.


Phenotypic markers for functional lymphocyte populations: a critical appraisal of current usage as disease markers and future prospects.

Abnormal immune function plays a role in a number of diseases, and measurement of immune function is an important role for Clinical Immunology laboratories (Chapel and Sewell, 1990; Miller et al., 1991; Rose et al., 1986; Stites, 1991). Tests for lymphocyte function tend to be slow and tedious, and to lack clinically useful discriminatory power; as a result their use in a clinical context is limited (see references cited above). On the other hand, the increasing numbers of monoclonal antibodies against lymphocyte membrane molecules has led to the use of markers as indicators of functional potential (Reinherz and Schlossman, 1982). This review examines the characteristics that make a clinically useful panel of markers, considers the kinds of questions that can be answered by marker or in vitro functional studies, reviews markers and functional assays in current use and proposes a panel of markers that may be worthy of further evaluation.


Noninfectious osteitis: part of the SAPHO syndrome.

SAPHO, a rare syndrome, is a recently suggested acronym for synovitis, acne, pustulosis, hyperostosis and osteitis. It encompasses many features which have been described in different but overlapping conditions. Not all of the syndrome components need to be present for inclusion in SAPHO to be justified, especially the dermatologic components. Two cases are described as examples. Clinicians should be aware of this rare disorder if positive early diagnoses are to be made in patients presenting with skeletal pain.


Long-term follow-up study of 164 patients with definite systemic sclerosis: classification considerations.

To evaluate the usefulness of recently proposed schemes of classification for systemic sclerosis an extensive cross-sectional study of a series of 164 consecutive patients with long-term systemic sclerosis was undertaken. There were 47 cases of proximal sclerosis, 93 of distal sclerosis and 24 of complete CREST syndrome. The study included clinical, visceral, immunological and follow-up data. In addition, a quantitative clinical score was calculated for each patient, thus providing indications for prognosis. Data were expressed according to three conventional systems of classification: The ARA system, the diffuse versus limited systemic sclerosis system and the early cutaneous involvement system. The most reliable indications of severe outcome were: proximal sclerosis, trunk skin involvement, presence of anti Scl 70 autoantibody, pulmonary and/or heart involvement and age. Diagnosis and prognosis were not generated by the same items. Prognosis indicators proved more accurate for groups than for individuals. Mortality was 1 death per 149 patient X years of follow-up from diagnosis. We conclude that the ARA criteria for classification should be recognized as a standard, but patients with complete CREST syndrome should be included in the distal group. Other systems of classification, principally 2-way versus 3-way criteria, allow different subsets of patients that correlate with prognosis and the severity of the disease, and could be used for therapeutic purposes.


Radiographic findings of spontaneous subluxation of the sternoclavicular joint.

Eight middle-aged women with spontaneous atraumatic subluxation of the sternoclavicular joint were evaluated with radiography and computed tomography. All patients were employed in occupations involving moderate to heavy physical labour, and no patients could recall a specific traumatic incident associated with onset of symptoms. In seven of the eight patients, the displacement of the medial clavicle was in a cranial direction; in four of the eight patients, there was an associated anterior subluxation, and in one patient, the subluxation was purely anterior. All five patients with an anterior component to the sternoclavicular subluxation had associated condensing osteitis of the clavicle. The sclerosis of the medial clavicle is possibly the result of chronic abrasion on the sternum and first costal cartilage in association with normal respiration and with upper extremity motion.


Thermography of frozen shoulder and rotator cuff tendinitis.

The role of thermography in the diagnosis of soft tissue lesions of the shoulder was evaluated by screening 28 patients with unilateral frozen shoulder and 86 patients with unilateral rotator cuff lesions. Index shoulders were then compared with the normal side. Differences in skin temperature distribution were found in 82% of subjects with frozen shoulder, nearly three-quarters of whom had reduced skin temperature. There was no consistent pattern of shoulder skin temperature found in rotator cuff tendinitis patients (49% normal, 28% reduced, 23% increased). Thermography can be helpful in the diagnosis of frozen shoulder but further studies are required to determine whether it is useful in other soft tissue shoulder lesions.


Clinical differences between ANA/anti-ENA positive or negative primary Sjögren's syndrome.

Fifty female patients with primary Sjögren's syndrome diagnosed according to the Copenhagen criteria were evaluated for both glandular and extraglandular involvement. They were divided into two groups based on the presence or absence of antinuclear and anti-ENA antibodies (ANA/anti-ENA). ANA/anti-ENA negative patients presented with milder and later glandular and extraglandular disease and required less frequent corticosteroid treatment. No significant differences were noted in extraglandular manifestations with the exception of leukopenia which was noted only in ANA/anti-ENA positive cases.


Effects of different regimes of corticosteroid treatment on calcium and bone metabolism in rheumatoid arthritis.

A clinical study of 30 patients with rheumatoid arthritis was undertaken in order to assess the acute effects of corticosteroids on calcium and bone metabolism. The patients were randomly divided into 3 groups. The first group was not treated with corticosteroids, the second group was treated with 3 oral pulses of 100 mg prednisolone and the third group received 3 intravenous pulses of 1000 mg methylprednisolone (MP) on alternate days during one week. In both steroid treated groups the serum parathyroid hormone concentration tended to increase. In the MP treated group an increase in the 1,25-dihydroxyvitamin D concentration after the first pulse was followed by a significant drop; this effect was also seen, but somewhat retarded and less distinct, in the orally treated group. In the MP treated group the urinary calcium excretion raised significantly 6 hrs after the first pulse and then dropped significantly. In all groups no changes were found in the serum calcium level and the urinary excretion of hydroxyproline. We conclude that, acute changes in calcium and bone metabolism occur during treatment with intravenous pulses of methylprednisolone and with oral pulses of prednisolone. These changes are small and reversible in a few days.


Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids.

The effects of dietary supplementation with n-3 fatty acids on the level of cytokines and complement activation in plasma from patients with rheumatoid arthritis were examined. Thirty-two patients with active rheumatoid arthritis were included in a 12-week double-blind, randomized study of dietary supplementation with n-3 fatty acids (3.6 g per day) or placebo. The cytokines were measured in plasma before and after treatment with fish oil or placebo. In general, cytokine values at the upper limits of the calculated normal areas were found. The Interleukin-1 beta concentration in plasma was reduced significantly after 12 weeks of dietary supplementation with fish oil (p < 0.03). No significant difference was observed in the placebo group. The tumour necrosis factor alpha activity in plasma did not change significantly (p = 0.167). No significant changes were observed in the degree of complement activation. The clinical status of the patients was improved in the fish oil group, but not in the placebo group, judged by Ritchie's articular index (p < 0.02). We conclude that dietary supplementation with n-3 fatty acids results in significantly reduced plasma IL-1 beta levels in patients with rheumatoid arthritis. Even though the cytokine levels were low, the anti-inflammatory effect of n-3 fatty acids could in part be explained by their ability to decrease cytokine production.


Rheumatoid nodulosis: a puzzling variant of rheumatoid arthritis.

Four patients with rheumatoid nodulosis are here described, together with a review of cases reported to date in the literature. This particular variant of rheumatoid arthritis (RA) is characterized by the presence of subcutaneous rheumatoid nodules, scanty or absent systemic manifestations and a clinically benign course. Joint involvement appears more commonly as palindromic rheumatism, although patients with arthralgia episodes alone and others with chronic polyarthritis have been described. Seldom reported up to now, a consideration of this entity may help to avoid diagnostic pitfalls and the use of aggressive therapy.


Vestibular syndrome in multiple myeloma: role of magnetic resonance imaging.

The authors report a case of multiple myeloma involving the temporal bone and responsible for a vestibular syndrome associated with hypoacusis. The lesion was best visualised by magnetic resonance imaging.


Possible causal association between ulcerative colitis and idiopathic thrombocytopenic purpura.

A 24-year-old Japanese male having ulcerative colitis and idiopathic thrombocytopenic purpura is described. When the symptoms of ulcerative colitis were manifest during his clinical course, the platelet life-span was shortened and the platelet associated IgG level was increased. Thus, causal association between the two diseases may be suggested.


A case of Raynaud's disease with uterine cancer producing interleukin-6.

A case of cervical cancer of the uterine producing interleukin-6(IL-6) in a patient who suffered from Raynaud's phenomenon is described. Her serum contained anti SS-A antibody. The cancer was removed surgically. High level of IL-6 activity was detected in the culture supernatant of the resected cancer cells. After operation, Raynaud's phenomenon had improved and anti SS-A antibody had disappeared. This case shows us that IL-6 produced by malignant tumour might induce autoimmune connective tissue disease-like symptoms.


Recurrent and migratory reflex sympathetic dystrophy syndrome.

A case of recurrent reflex sympathetic dystrophy syndrome (RSDS), involving consecutively three extremities in an otherwise healthy adult is described. In a period of four years follow-up she presented three RSDS episodes occurring without precipitating events and involving consecutively both lower legs and the left hand. The RSDS resolved without sequelae after treatment with physiotherapy and diclofenac in an early phase. RSDS is an often unrecognized entity which appears mostly confined to a single limb. Recurrent forms have also been described, sometimes with a migratory pattern. Involvement of upper and lower limbs in the same patient is thought to be infrequent.


Behçet's syndrome and factor XII deficiency.

Several mechanisms have been proposed to explain thrombotic tendency in Behçet's syndrome. We report the case of a 43-year old woman presenting retinal-vein thrombosis, factor XII deficiency and Behçet's syndrome. This kind of association has thus far never been reported. Factor XII deficiency is known to possibly induce various types of thrombosis and might explain the prevalence of ocular symptoms in our patient.


Bacterial pyomyositis in a patient with a multiple myeloma.

Pyomyositis is relatively rare in regions with a temperate climate. The most common aetiologic agent is staphylococcus aureus. Most patients with pyomyositis from temperate regions involve immunocompromised states. Because of the rarity, it is often initially misdiagnosed. Computed tomography scan is considered the most helpful tool for the diagnosis of pyomyositis. We present a case in a patient with multiple myeloma.


Localized nodular myositis. A paraneoplastic phenomenon.

Localized nodular myositis was recognized in an elderly man six months prior to the diagnosis of Hodgkin's disease. Meticulous search of the muscle specimen failed to disclose tumorous involvement. The possible paraneoplastic nature of localized nodular myositis in this patient is discussed.


Rheumatoid arthritis, corticosteroid therapy and Kaposi's sarcoma: a coincidence? A case and review of literature.

We describe a 68-year-old woman suffering from rheumatoid arthritis treated with low doses of prednisone who developed Kaposi's sarcoma (KS). This patient was not affected with AIDS, and two years previously, her sister had also complained of KS. In the literature only 8 rheumatoid arthritis patients who developed KS during steroid therapy have been reported. We present a review of the literature and question the responsibility of corticosteroids and autoimmune diseases as the cause of KS.


Ankylosing spondylitis and sarcoidosis--coincidence or association? Case report and review of the literature.

We report a 25-year-old woman presenting with sarcoidosis and bilateral sacroiliitis. Her sarcoidosis related symptoms (malaise, cough and dyspnoea) improved dramatically under treatment with steroids but severe back pain persisted. Only seven similar cases have been described over the last 40 years and the question of a possible association between the two diseases has been raised. However, prevalence data from the literature and the apparent lack of genetic links are better arguments for coincidence than for association.


Radiological vignette. Insufficiency fracture of the acetabulum.

An insufficiency fracture (IF) involving the acetabulum is presented. This fracture occurred in a 67-year-old woman who had been hysterectomized and oophorectomized 27 years earlier for a carcinoma of the uterine cervix, and who had received external pelvic irradiation. This IF location has been rarely described earlier, and its awareness should preclude unnecessary aggressive diagnostic procedures especially in patients with osteoporosis and previous pelvic radiotherapy.


[An open non-comparative study of the efficacy and tolerability of sultamicillin in the therapy of respiratory infections in childhood].

Forty-eight children (25 males + 23 females), mean age 3.5 years +/- 2.6 (range 1-11), were treated for the following respiratory infections: pharyngotonsillitis (9), bronchitis (18), bronchopneumonia (14), asthmatic bronchitis (4) and pneumonia (3). The average duration of treatment was 5.3 +/- 2.0 days (range 3-13). Sultamicillin was administered at the dose of 50 mg/kg/day. Patients with fever experienced a defervescence on the second day of therapy. Forty-six children (96%) showed a good clinical response. The tolerability of the drug was excellent or good in 93.8% of the cases.


[Ocular pathology in HIV infection].

The above short note underscores the importance of ocular complications in HIV infection. These syndromes are either isolated or concomitant with CNS involvement but frequently they do not receive due consideration.


[Telethermography in the diagnosis of lumbo-sciatica syndromes].

Thermal maps of the lumbo-sacral and gluteal regions and of the lower limbs were obtained with telethermography in 30 subjects suffering from painful lumbo-sciatic syndromes in order to assess whether there were differences of thermal index between painful and opposite side, and to evaluate the telethermographic patterns of the irritative and deficitary forms. Among 25 patients with lumbo-sciatalgia in the irritative or early stage, 16 showed hypothermia of the affected side; in three of the five patients in the deficitary stage, hyperthermia of the affected side was observed while two did not show changes of the thermal gradient. The authors stress the importance of telethermography and suggest that this method, which is not costly, non-invasive and easily reproducible, should be used to complete diagnosis of and to monitor lumbo-sciatalgic syndromes.


[Efficacy and tolerability of ketoprofen lysine salt foam for topical use in the treatment of traumatic pathologies of the locomotor apparatus].

In this study the authors evaluated the efficacy and tolerability of a foam of 15% ketoprofen lysine salt versus placebo in patients with articular traumas, pains and strains, distortions etc. All parameters considered were statistically significantly decreased after 7 days of active treatment as compared to placebo. Pain score decreased significantly at pressure (p < 0.001), pain on active movement (p < 0.005), pain on passive movement and pain at rest. Efficacy of the active foam was graded as satisfactory in 81.7% and its tolerability in 92.7% versus 44% and 29% with placebo respectively. Patients reported high acceptability (89%) of the new foam formulation. No systemic or local side effects were observed or reported. The 15% ketoprofen lysine salt foam for topical use can be considered an effective antiinflammatory and analgesic drug for the treatment of minor orthopedic and traumatic disorders, and was found to be perfectly tolerated.


[Recent experience in the short-term etizolam treatment of irritable colon syndrome].

Twenty-two subjects (8 males, 14 females, mean age 36 years, range 21-57) with symptoms of diffuse pain or fullness in a lower abdominal quadrant, without repercussions on general health but with chronic anxiety of which the subjects complained or which emerged during confidential conversation with the physicians, were enrolled in our outpatient department for liver and gastroenterologic pathology at the Institute of Internal Medicine and Metabolic Disorders, II Faculty of Medicine, Naples University. After an average 30-day wash-out period, patients were treated with etizolam, a new psychoactive drug for somatized anxiety. Mean dosage and duration of treatment were 1 tablet twice daily for 25 days. Painful symptoms disappeared in 16.3% of patients, decreased in 38.3% and remained stationary in 22.7% and became worse in 22.7%. Number of bowel motions decreased in 14 patients (63.6%, from an average of 2.04 to 1.56). It can therefore be concluded that etizolam treatment was effective in subjects with colon disorders accompanied by chronic anxiety syndrome or that became acute as result of stressful socio-economic or affective situations or personal disappointment.


[Silent myocardial ischemia with raised ST tract in 2 octogenarian patients without ischemic cardiopathy].

The authors describe two recently observed cases of silent angina with ST segment elevation. The patients, both 80-years old, were submitted to 24-hour Holter examination to account for recurrent episodes of dizziness. The examination revealed silent angina with ST elevation concentrated mainly in the late evening and morning hours, accompanied by accelerated heart rate. Treatment with low diltiazem doses was completely successful.


[Role of magnetic resonance in the evaluation of thrombosis of large thoraco-abdominal vessels].

Magnetic resonance (MR) has been found to be a method suitable for the study of the vascular system since it permits to distinguish between moving (circulating blood) and static (thrombi, atherosclerotic plaques, intimal flaps) tissues. The sequences used for the evaluation of thrombi are Spin Echo (SE) and Gradient Echo (GE). If both sequences are used the diagnosis of thrombosis is considerably more reliable. The limits of the technique are represented by spatial resolution which is not optimal and makes the evaluation of thrombi in small or medium-size vessels difficult; further, small or non occlusive thrombi may be difficult to identify. Nowadays, with the technique of angiography with magnetic resonance (AMR) it has become possible to obtain high quality images of the vessels of the head, neck, abdomen and limbs. Further improvements of the AMR technique are likely to replace diagnostic angiography.


Neglected organization and management issues in mental health systems development.

Fragmented and often uncoordinated public services for the more severely mentally ill are often characteristic of the current U.S. mental health system. The creation of local mental health authorities has been promoted as part of a solution, as has happened in Wisconsin at the county level and is championed in the ongoing Robert Wood Johnson Foundation funded innovative service sites for severely mentally ill adults. There are indications that these innovative mental health authorities will fall short of fulfilling their promise. Basic principles from the management and organizations literature are used to identify several organization and management issues that may have been neglected. These include resource management, attention to system goals, monitoring and feedback, and the promotion of desirable interorganizational cultures.


Predicting psychiatric symptoms among homeless people.

Multiple regression was used to predict psychiatric symptoms among homeless people. The following variables were significant predictors of psychiatric symptoms: current life satisfaction, previous psychiatric hospitalization, the number of stressful life events, social support, problem drinking, and childhood unhappiness. The results are discussed in terms of their policy and practice implications, particularly the need for crisis intervention services and for dual-diagnosed clients.


Social support and quality of life of community support clients.

Two aspects of social support, availability and adequacy, were assessed for 729 severely mentally ill adults enrolled in seven state-supported Community Support Services (CSS) programs as part of repeated questionnaire surveys nine months apart. Perceived quality of life interviews with the clients were also conducted at both times. These interviews included the Bradburn Positive and Negative Affect Scales and the Satisfaction with Life Domains Scale (SLDS). Availability of social support was significantly correlated with positive affect over time, but not with negative affect at either point. Inadequacy of social support was significantly related to negative affect at both assessments. Both availability and adequacy of social support were significantly related to the SLDS at each time. Change in satisfaction with life domains was found to be related to both availability and, to a lesser degree, with adequacy of social support.


Informal systems of care for the chronically mentally ill.

The purpose of this paper is to describe the structure and functioning of informal caregiving systems of community-based chronically mentally ill individuals. From a sample of 409 family member reports, 150 caregiving systems are described in terms of size, composition and division of caregiving labor. Results show that these systems are about as large as those found for elder caregiving systems, that women and relatives predominate as caregivers, that there is considerable diversity in the types of caregivers and that size and composition are related to the division of labor observed in these systems.


Clinical issues in social network therapy for clients with schizophrenia.

Social networks are viable foci for therapeutic interventions. A social network therapy program for clients with schizophrenia was developed by a community-based mental health agency. This paper presents four of the most common clinical issues encountered and illustrates each with a case example.


A comparison of how families and their service providers rate family generated quality of service factors.

This paper presents a method which was utilized to obtain family consensus around the criteria which should be used to evaluate family support programs. Twelve family members of persons with developmental disabilities were selected in each of six different sites to participate in a group process to identify the factors which distinguish quality family support programs. Content analysis of the results of the six meetings resulted in a final list of 15 quality factors. Two hundred and sixty one families and their family support coordinators (N = 65) were asked to rate the importance of each factor on a 10 point scale. Analysis revealed that there was high agreement between families and their coordinators on the importance of all 15 factors. The applicability of the method used to obtain family consensus regarding evaluation criteria for community mental health agencies is discussed.


The quality assurance dilemma in psychiatry: a sociological perspective.

Tensions between mental health practitioners and their colleagues in quality assurance can be reduced. A sociological view of the evolution of psychiatric practice from the doctor-patient dyad to the therapist-patient-third party triad and of the discontinuity between the new structure and the culture of professional practice frames the discussion. Drawing on approaches to quality developed in business settings, it is argued that third parties as well as patients are "customers" and that a different approach to quality is appropriate to each. Crosby's methodology is recommended as relevant to the management of relationships with third parties.


Triacylglycerol biosynthesis in bovine liver and subcutaneous adipose tissue.

1. Adipose tissue from Angus and Brahman steers incubated with [1-14C]palmitate in the absence and presence of glucose exhibited a greater rate of lipid production than liver (P < 0.05). 2. Homogenates of adipose tissue used in the glycerol-3-phosphate acyltransferase assay exhibited a greater glycerolipid specific activity (nmol lipid/mg protein/30 min) when compared to liver (P < 0.05). 3. The inverse was true for liver homogenates when calculated for tissue activity (nmol lipid/g tissue/30 min). 4. Lysophosphatidate was produced in greater (P < 0.05) amounts than all other glycerolipids in the glycerol-3-phosphate acyltransferase assay. 5. The activity of phosphatidate phosphohydrolase in liver homogenates displayed greater rates than their respective adipose tissue homogenates. 6. Diacylglycerol acyltransferase activity was greater in adipose tissue homogenates compared to liver homogenates.


Purification and biochemical properties of calmodulin in Entamoeba histolytica and its distribution during secretion of electron-dense granules.

1. Calmodulin (CaM) was detected during secretion of electron-dense granules by Entamoeba histolytica trophozoites with immunofluorescence. 2. It was purified to apparent homogeneity by chromatography with a yield of 2.26 micrograms of calmodulin/mg of protozoan protein. Purity was established by gel electrophoresis. 3. The parasite calmodulin has properties characteristic of calmodulin isolated from other eukaryotes: an apparent molecular weight of 19 or 17 kDa in presence of EGTA or CaCl2, respectively, activation in a calcium dependent manner of bovine heart cyclic nucleotide phosphodiesterase, and its UV spectrum.


The critical role of asparagine 502 in post-translational alteration of protein 4.1.

1. Protein 4.1 in most mammalian red cells exhibits a post-translational conversion of 4.1b to 4.1a, except for feline protein 4.1, which lacks this alteration. 2. Our previous study provided evidence that protein 4.1b in human red cells is converted to 4.1a by deamidation of a specific asparagine (Asn) residue at position 502, suggesting that the post-translational change of 4.1b to 4.1a depends on the primary structure of the protein at the site of deamidation. 3. To confirm this hypothesis, proteolytic fragments corresponding to the deamidation site of human protein 4.1 were purified from canine and feline erythrocyte protein 4.1 and analyzed for their amino acid sequences. 4. Two proteolytic peptides, D7 and D9 derived from canine protein 4.1, both corresponding to the human sequence Thr492-...-Asn (or Asp)502-...-Lys505 showed the same sequence, Thr-Gln-Thr-...-Lys, except that the 11th residue equivalent to the 502nd amino acid was Asn in D7 while it was Asp in D9, indicating that deamidation occurs at the same position in canine protein 4.1 as in humans. 5. However, substitution of Ser for Asn at this position was observed in feline protein 4.1. 6. These results demonstrate that Asn502 has a critical role in post-translational conversion of 4.1b to 4.1a in mammalian red blood cells.


Chicken leg muscle alpha-connectin as studied by a monoclonal antibody to the 1200 kDa fragment.

Chicken leg gracilis muscle contained only alpha-connectin (ca 3000 kDa) without beta-connectin. When myofibrils were kept standing for 20 hr at 4 degrees C, alpha-connectin was degraded to beta-connectin (ca 2000 kDa) and 1200 kDa peptide. The latter was prepared from myofibrils and purified by gel filtration in the presence of SDS. A monoclonal antibody, alpha 7, to this 1200 kDa fragment was prepared. The antibody reacted with the 1200 kDa fragment and its mother molecule alpha-connectin, but not with beta-connectin. Immunoelectron microscopy using alpha 7, as well as other antibodies to chicken breast muscle beta-connectin, revealed that the 1200 kDa peptide covered the portion of alpha-connectin from the Z line to the N2 line region in the I band of chicken leg gracilis muscle sarcomeres. The results were in good agreement with those observed in rabbit skeletal muscle.


Comparative characterization of liver glycogen metabolism in rat and guinea-pig.

1. Guinea-pig liver contained more phosphorylase in the active (phosphorylated) form and less synthase in the active (dephosphorylated) form when compared with rat liver. 2. Activities of cyclic AMP-dependent protein kinase and Ca(2+)-dependent phosphorylase kinase were the same in rat and guinea-pig livers. 3. Activities of phosphorylase phosphatase and synthase phosphatase in the extract and glycogen plus microsomal fraction of guinea-pig liver were significantly lower than those of rat liver. 4. The existence of inhibitor-1 in the liver of guinea-pig can maintain a lower activity of type-1 protein phosphatase, especially when inhibitor-1 is phosphorylated by cyclic AMP-dependent protein kinase.


A comparative study of Drosophila phenylalanine hydroxylase with a natural and a synthetic tetrahydropterin as cofactor.

1. Phenylalanine hydroxylase activity has been analyzed in Drosophila melanogaster using as cofactors the natural tetrahydropteridine 5,6,7,8-tetrahydrobiopterin (H4Bip) and the synthetic one 5,6-dimethyl-5,6,7,8-tetrahydropterin (H4Dmp). 2. The apparent Vmax and KM for substrate and cofactor showed that the enzyme has two times more affinity for the substrate when H4Bip is the cofactor in the reaction. Similarly to what was found with purified rat liver phenylalanine hydroxylase, H4Bip was the most effective cofactor, leading to 4-5 times more activity than that obtained with H4Dmp. 3. With the natural cofactor H4Bip, no activation of the enzyme with Phe was necessary (in contrast to mammalian phenylalanine hydroxylase), and this tetrahydropteridine inhibits phenylalanine hydroxylase activity when the enzyme is exposed to it before phenylalanine addition. With the synthetic H4Dmp, both types of preincubations led to an increase of phenylalanine hydroxylase activity. 4. The enzyme is highly unstable compared to mammalian phenylalanine hydroxylase, even at -20 degrees C. 5. Thorax and abdomen extracts caused significant inhibition of phenylalanine hydroxylase activity from third instar larvae or newborn adult head extracts, when assayed with the synthetic cofactor H4Dmp. This inhibition did not happen with H4Bip. The presence of the pteridine 7-xanthopterin in adult bodies was not the cause of this inhibition.


Purification of a novel heterodimer from shark (Carcharhinus plumbeus) serum by gel-immobilized metal chromatography.

1. Resolution of the fraction of sandbar shark (Carcharhinus plumbeus) serum that was soluble in 50% saturated ammonium sulfate by gel-immobilized metal-affinity chromatography allowed the isolation of a novel disulfide-bonded heterodimer of intact mass 70 kDa. 2. Following reduction, the molecule could be resolved into two chains of apparent mass 36 and 24 kDa. 3. The molecules were glycoproteins as determined by an observed reduction in molecular weight following enzymatic glycosylation. 4. The two separate chains were related to one another on the basis of amino-acid composition analysis and by comparison of the N-terminal amino acids (seven out of 10 identities). 5. The exact relationship of this molecule to characterized heterodimers of higher vertebrates is unknown. 6. Cross-linked agarose-acetate was synthesized and proved to be an efficient concentrating agent and also a hydrophobic interaction adsorbant.


Alterations to the permeability of plant and animal mitochondria submitted to Ca2+ releasing agents.

1. Mitochondria from different rat tissues and from plants were compared as regards their sensitivity towards Ca2+ in the presence of different Ca2+ releasing agents, and the phospholipase A2 activity was evaluated in the different mitochondrial preparations. 2. The mitochondria were exposed to Ca2+ and an oxidant such as t-butylhydroperoxide or diamide or to Ca2+ and inorganic phosphate, and plant mitochondria were seen to be much more resistant than liver, brain or kidney mitochondria of rats to the deleterious effects of these agents. 3. The phospholipase A2 activity is not directly involved in the alterations of the mitochondrial inner membrane permeability within the first 10 min of incubation under our experimental conditions. 4. The protection conferred by ATP and Mg2+ against Ca2+ efflux from mitochondria or the decrease in the mitochondrial transmembrane electrical potential was also observed under our experimental conditions, but cannot be attributed to an enhancement of the reacylation of lysophospholipids resulting from the phospholipase A2 activity.


The biological properties of venoms from juvenile and adult taipan (Oxyuranus scutellatus) snakes.

1. The biological properties of four venom pooled samples from adult taipan (Oxyuranus scutellatus) snakes and one pooled venom sample from six juvenile taipan snakes (11 months old) were compared. 2. The intravenous LD50 (median lethal dose), procoagulant activity and enzymatic activities of the juvenile venom were not significantly different from those of the adult venoms. 3. The juvenile and adult venoms exhibited similar polyacrylamide gel electrophoretic (PAGE) and SDS-PAGE patterns, indicating that they possessed a similar protein composition. 4. The results suggest that there is no significant age-dependency in the biological properties of taipan venom.


Inter- and intra-specific differences in serum proteins of different species and subspecies of zebras.

1. Serum proteins of Equus grevyi, E. zebra hartmannae, E. burchelli boehmi, E. b. chapmanni and E. b. antiquorum were studied using starch-gel electrophoresis, 1-D polyacrylamide-gel electrophoresis, inhibitions of trypsin and chymotrypsin, immunoblotting, and specific staining for esterase. 2. Clear species-specific patterns were observed in albumin, transferrin, and for E. grevyi in protease inhibitor-1. Specific esterase was detected only in E. z. hartmannae. 3. Protein polymorphism was found in all studied species: E. grevyi--transferrin; E. z. hartmannae--protease inhibitor-1; E. b. boehmi--albumin, GC, transferrin, protease inhibitor-1, protease inhibitor-T; E. b. chapmanni--albumin, GC, transferrin, protease inhibitor-1; E. b. antiquorum--GC, transferrin, protease inhibitor-1. 4. Phenotype patterns of the polymorphic proteins were indicative of simple codominant inheritance. Further studies of polymorphism of protease inhibitor-2 and variability of protease inhibitor-X are needed. 5. alpha 1B glycoprotein in all zebra species was monomorphic. 6. The main transferrin components and alpha 1B glycoprotein of zebra (E. b. boehmi) were characterized for terminal sialic acid content.


Tissue distribution of insulin-like growth factor receptors in the turkey.

1. The distribution and relative insulin-like growth factor (IGF) binding capacities of membranes derived from 14 tissues of the turkey were examined. 2. Affinity cross-linking analyses using [125I]IGF-I and [125I]IGF-II with membranes derived from the liver, pectoralis major muscle, gizzard, heart and brain indicated that both IGFs interact with only type-I IGF receptors on these tissues. 3. There was no evidence for the existence of a type-II IGF receptor in any tissue. 4. Although considerable variation was detected in the molecular weights of the IGF receptor alpha subunits between tissues (112.2-132.9 kDa), these differences did not appear to influence receptor-ligand affinities.


Intestinal disaccharidases in the house musk shrew, Suncus murinus: occurrence of sucrase deficiency.

1. Disaccharidase activities of the small-intestinal brush border membrane were studied in six laboratory lines of the house musk shrew, Suncus murinus. 2. Sucrase activity was detected in all shrews of one line, but not in any shrew of three lines. In the other two lines it was found in some shrews, but not in the others. 3. Maltase, isomaltase, trehalase and lactase activities were found in all shrews of all the lines examined. 4. Sucrase was normally associated with isomaltase to form an enzyme complex. 5. Detergent-solubilized isomaltase, whether associated with sucrase or not, was inhibited by antibodies against rabbit sucrase-isomaltase to almost the same extent as the rabbit one, suggesting that isomaltase is not affected by a mutation(s) in sucrase.


North-south regional variation in phospholipase A activity in the venom of Crotalus ruber.

1. Twenty-seven individual venoms from the rattlesnake species Crotalus ruber from different regions were comparatively analyzed by reverse-phase HPLC and analyzed for phospholipase A (PLA) content using a polarographic assay. 2. Two fractions containing PLA activity were detected by HPLC in the venoms of all the C. ruber specimens from southern Baja, Mexico, but specimens from southern California, U.S.A., were lacking corresponding fractions and were extremely low or lacking in PLA activity in their venoms. 3. The north-south regional variation in PLA content in C. ruber venom does not correlate with the north-south ranges (based on external morphology) of the subspecies C. ruber ruber and C. ruber lucasensis.


Nucleotide sequence and presumed secondary structure of the internal transcribed spacers of rDNA of the pea aphid, Acyrthosiphon pisum.

1. Internal transcribed spacer (ITS) 1 and ITS 2 of rDNA of the pea aphid, Acyrthosiphon pisum consisted of 229 and 280 nucleotides, whose G+C contents were 70 and 74%, respectively. 2. Secondary structure models constructed for the ITS 1 and ITS 2 suggested that certain structural motifs have been conserved in these regions despite extensive divergence in nucleotide sequence due to species.


Epidermal growth factor (EGF) stimulation of ATP citrate lyase activity in isolated rat hepatocytes is age dependent.

1. The effect of epidermal growth factor (EGF) on ATP citrate lyase activity was determined in freshly isolated hepatocytes from rats of different ages as a function of incubation time, EGF concentration and hepatocyte density. 2. The activity of this enzyme was responsive to both dose and time of incubation of EGF with a two-fold increase in ATP citrate lyase activity and a half-maximal effect between 10(-12) and 10(-11) M. 3. EGF effects were detectable by 5 min. 4. The age of the rats had a strong effect on the magnitude of the EGF effect with ATP citrate lyase activity in younger (8 weeks) rats being more responsive than in older (14 weeks) rats.


Purification, biochemical characterization and N-terminal sequence of a serine-protease with chymotrypsic and collagenolytic activities in a tropical shrimp, Penaeus vannamei (Crustacea, Decapoda).

1. Two chymotrypsin variants, with collagenolytic activities, were purified from the hepatopancreas of Penaeus vannamei using radioactive protein as the substrate. 2. These proteases are very close as far as amino acid composition, molecular weight, inhibitors studies and specificity against small synthetic substrates are concerned. 3. N-terminal amino acid sequences of both variants are identical and are very close to other known crustacean serine proteases.


Characterization of the eggshell of Haemonchus contortus--I. Structural components.

1. By transmission electron microscopy, the eggshell of Haemonchus contortus was seen to be similar to previously studied nematodes, with an outer vitelline layer bounded by a trilaminate membrane, a broad medial region, containing chitin, and an electron dense basal region, containing lipid and protein. 2. Exposure of Haemonchus contortus eggs to proteases resulted in disruption of the shell with removal of components of the outer, medial and basal regions. Exposure to chitinase depleted fibrillar components of the medial region of the shell, while collagenase had no effect. 3. Chloroform/methanol extraction of fresh eggshells caused a minor condensation of the outer, vitelline layer and some depletion of the basal layer. 4. After normal hatching, shells appeared similar to those treated with protease and chitinase, but also lacked the basal, lipid layer. 5. Extracts of isolated unhatched eggshells and hatched eggshells, and extracts of biotin-labelled whole fresh eggs showed three major protein bands when run on sodium dodecyl sulphate-polyacrylamide gels indicating that these three proteins are most likely structural in nature and do not participate in the release of the larva from the eggshell. 6. Biotin-labelled protein bands were degraded by proteases and chitinase, but not collagenase or lipase.


Identification of vitellogenin in the little skate (Raja erinacea).

1. Vitellogenin was isolated from mature female skates by selective precipitation with MgCl2/EDTA followed by chromatography on DEAE-cellulose columns. 2. A single monomer of approximately 205 kDa was identified on 6.0% SDS-PAGE gels. 3. In addition, isolation of yolk proteins with ammonium sulfate yielded proteins of 94 and 38 kDa (putative phosvitins) and putative lipovitellins of ca 105, 91 and 67 kDa. 4. In vivo phosphate incorporation in female and male skates implanted with estradiol indicated that vitellogenin was phosphorylated. 5. Total protein phosphate incorporation was significantly higher in females than male skates. 6. In male skates treated with estradiol, phosphate incorporation increased from 2 days after implantation to a maximum at approximately 11 days after implantation. 7. Determination of the rate of disappearance of 32P-labeled protein suggests a half-life of ca 200 hr in normal female skate plasma.


Putative apolipoprotein B-100 in the freshwater turtle Chrysemys picta: effects of estrogen and progesterone.

1. The isolation and purification of a putative apolipoprotein B-100 in the plasma of the freshwater turtle Chrysemys picta is described. 2. The protein was purified through differential ultracentrifugation and subsequent Sepharose 6B column chromatography. 3. The molecular weight of the protein determined by electrophoresis was approximately 350 kDa. 4. An antibody to chicken apolipoprotein B-100 specifically recognizes this 350 kDa protein in Western blots, suggesting its identity with apolipoprotein B-100. 5. An antibody to the putative Chrysemys apolipoprotein B-100-like protein was developed and used in an ELISA to quantitate protein levels in plasma. 6. Acute estrogen treatment increased levels of apolipoprotein B-100 (7.64 +/- 0.79 mg/ml plasma) over that of control animals (5.07 +/- 1.74 mg/ml plasma). 7. In contrast, chronic estrogen treatment reduced apolipoprotein B-100 significantly to 2.94 +/- 0.53 mg/ml plasma (P < 0.05).


A comparative study on ceramide composition of cetacean brain gangliosides.

1. Ceramide composition and N-glycolylneuraminic acid content of gangliosides from gray and white matters and myelin of cerebrum and cerebellum were analyzed in eight species belonging to the suborder Odontoceti and two species to Mystacoceti. 2. The most characteristic feature was high contents of C20:0 (10-40%) and C24 species (5-40%). 3. Content of hydroxy fatty acid of C24 species was higher in cerebellum (5-20%) than cerebrum (0-3%). 4. Major component of long-chain base was dC18:1 (70-90%). 5. N-glycolylneuraminic acid was found in sperm whale, Dall's porpoise and killer whale (0.1-1.7%).


Species-related variations in tissue antioxidant status--I. Differences in antioxidant enzyme profiles.

1. Antioxidant enzyme activity profiles in red cells of man, rabbit, quail, pig and rat have been investigated and found to exhibit striking differences. 2. No direct correlations between activities of "functionally coupled" enzymes (superoxide dismutase/catalase and glutathione peroxidase/glutathione reductase) were apparent, suggesting their independent regulation. 3. However, activities of red cell catalase and glutathione peroxidase in the various species studied were inversely correlated. 4. This was most evident in quail red cells, which showed negligible catalase activity but the highest levels of glutathione peroxidase of all the species examined. 5. A significant positive correlation between catalase and glutathione reductase activities was also demonstrated. 6. This may be relevant to the suggestion that the binding of NADPH to catalase may serve to decrease the intracellular inactivation of this reducing cofactor which may be limiting in the glutathione reductase reaction. 7. Basal levels of glutathione, which have been claimed to be limiting for the glutathione peroxidase reaction, were found to correlate positively with the activity of this enzyme in red cells. 8. Myocardial tissues also exhibited species-related differences in antioxidant enzyme profiles but these did not bear any obvious relationship to patterns observed in the corresponding red cells.


Species-related variations in tissue antioxidant status--II. Differences in susceptibility to oxidative challenge.

1. In order to investigate possible species-related variations in antioxidant capacity, the susceptibility of red cells from various species (e.g. rat, rabbit, pig and quail) to depletion of glutathione (GSH) and formation of malondialdehyde (MDA), an indirect measure of lipid peroxidation, following in vitro oxidative challenge with t-butylhydroperoxide (tBHP) has been examined. 2. Marked differences in sensitivity were found, although the relative order of susceptibilities varied depending on the index of oxidation used. 3. For example, pig erythrocytes showed the highest sensitivity to depletion of GSH but the greatest resistance to tBHP-induced MDA formation. 4. Red cell susceptibility to oxidative stress under the experimental conditions used was not predictable from basal levels of GSH or from the activities of antioxidant enzymes, suggesting a prominent role of non-enzymatic antioxidants. 5. Species-dependent differences in antioxidant capacity were also found to extend to myocardial tissue homogenates and some degree of parallelism was noted with tBHP-induced MDA formation in red cells of the same species. 6. Thus, the relative resistance of both tissues from pig contrasted with the high susceptibility of red cells and myocardium from rat and quail. 7. This parallelism allows the suggestion that the functional consequences of antioxidant interventions might be discernible from measurements involving red cells. 8. Our findings may have potentially important implications in the interpretation and comparison of data obtained with experimental models of disease states in which oxidative processes are implicated when differences in species are involved.


Purification and characterization of a humoral opsonin from the solitary urochordate Styela clava.

1. We have previously identified opsonic activity in the plasma of the solitary urochordate, Styela clava. 2. Here, we report the purification and further characterization of the opsonic molecule. 3. Two purification methods were employed. 4. Gel filtration yielded one strongly opsonic fraction that contained a single, electrophoretically-resolved protein. 5. Opsonic activity was dose-dependent and sensitive to tryptic digestion and heat denaturation. 6. SDS-PAGE and calibrated gel filtration indicated the opsonic protein was a 17.5 kDa monomer while isoelectrofocusing indicated a single pI of 7.0. 7. In an alternative procedure, a similar opsonic activity and protein were isolated by affinity purification using whole yeast cells.


Analysis of the causes of the suppression of oxidative phosphorylation and energy-dependent cationic transport into liver mitochondria of hibernating gophers, Citellus undulatus.

1. The causes of the suppression of oxidative phosphorylation and energy-dependent cationic transport into liver mitochondria of hibernating gophers have been analysed. 2. The decrease of the ATP synthesis rate and suppression of the energy-dependent K(+)- and Ca(2+)-transport into mitochondria during hibernation has been found to be mainly related to a delta psi decrease in mitochondria of hibernating gophers. 3. The increase delta psi upon incubation of the mitochondria of hibernating animals in a hypotonic medium results in an essential acceleration of ATP synthesis and energy-dependent cationic transport.


On AR modelling for MEG spectral estimation, data compression and classification.

The use of the autoregressive (AR) model for magnetoencephalogram (MEG) processing is examined and compared to other methods. Spectral estimation, classification and data compression of MEG signals are studied. In application to spectral estimation the AR model is compared to the classical modified periodogram method. Also, AR modelling appears to perform very successfully when used for the classification of normal and epileptic MEG signals. Finally, the 17:1 to 23:1 data compression achieved by AR modelling, along with the above-mentioned advantages, render it suitable for storage applications. For comparison, the method of feature selection via orthogonal expansion is used as a tool to achieve data reduction. It is seen that while effective, this is less drastic than the compression of data volume achieved by AR modelling.


Numerical phase algorithm for decompression computers and application.

Present generation decompression computers employ a simplified algorithm, limiting dissolved gas build-up in tissue and blood according to a method proposed by Haldane 80 years ago. Such a model works well for single dives, but is usually liberal and theoretically incomplete for multiple exposures within 24 hr spans. Using the critical phase hypothesis in a bubble model, we have extended the classical model of Haldane to multi-exposures. This model is discussed, and a decomputer algorithm described for multi-diving. The focus is permissible bubble excess, not just dissolved gas per se, with phase constraints affecting all tissues, fast and slow, and requiring a systematic lowering of repetitive tissue tensions. Deep repetitive and shallow multi-day exposures are impacted most by the procedure. Within nucleation theory deeper-than-first dives are also treated. A set of multi-diving fractions, xi, accounting for micronuclei excitation and regeneration, reduced bubble elimination in repetitive activity, and coupled effects on tissue tension, are proposed, with xi representing a set of multiplicative factors (less than one) applied to critical tissue tensions for multi-exposures. These factors affect repetitive activity over short time spans, deeper-than-previous and continuous multi-day activities, compared to standard computer software, and are easily encoded into existing decompression meters, potentially extending their range and flexibility over exposure regimes.


Automatic computer analysis of transients in EEG.

The electroencephalogram (EEG) is often used for the diagnosis of diseases and functional disturbances in the brain. In this paper, new algorithms developed for the automatic detection of transients in EEG are described. The single spike, and spike and wave bursts, both of which are abnormal phenomena associated with epileptic activity are considered. The algorithms for detecting these transients were tested using real EEG data. The transient detection is enhanced by two classification algorithms: patient-independent analysis and patient-dependent analysis. In the patient-independent analysis, multiple reference templates are generated from a patient population and for the patient-dependent analysis, the spikes from the patient's own EEG recording is used as reference. The description of the algorithms and their performances are presented.


Development and testing of a PC-based system with menu-driven software for evaluating lung function in ICU patients.

This paper describes a portable PC-based system for measuring respiratory system resistance (Rrs) and dynamic lung compliance (Cdyn) in intubated and mechanically ventilated patients. A pneumotachometer placed immediately proximal to the endotracheal tube measures flow, and a pressure catheter with its tip at the distal end of the endotracheal tube measures lateral airway pressure. The software is menu driven and allows the user to select from options including patient information display and entry, data collection, data editing, and waveform display. Up to ten consecutive breaths can be analyzed per run. Rrs and Cdyn are calculated on a breath by breath basis. Results are displayed to the screen, output to the system printer, and written to a user-specified ACSII data file. The system was tested by measuring resistance and compliance in a model of the lung, and results compared with those calculated from analog signals. It was then used to make measurements in intubated post-operative patients. Results were comparable to those previously reported in intubated ICU patients without primary lung disease. We conclude that our system provides reliable measurements of lung mechanics in the intubated patient, and represents an inexpensive and more versatile alternative to microprocessor-based ventilator systems currently being marketed.


A fitness analysis system with an intelligent interface.

This paper describes the development of a system with an intelligent interface for analysis of physiological correlates of athletes' physical performance capacities. The system improves the interface between the physiologist and the coach and provides scientific information in a systematic and coherent fashion. The recommendations provided are based on the results of a series of physiological tests. The implementation of the system is described with emphasis placed on recognition of the internal structure of the knowledge, independence from a particular shell, design for future expansion and maintenance and the integration with existing information resources.


Validation of the medical expert system PNEUMON-IA.

The present study validates the expert system PNEUMON-IA. The aim of PNEUMON-IA is assessing the etiology of community-acquired pneumonias from clinical, radiological, and laboratory data obtained at the onset of the disease. Validation was performed using data from medical records of 76 patients with proven clinical diagnosis of pneumonia. The etiological diagnoses provided by PNEUMON-IA were compared to those established by five specialists unrelated to the development of the expert system. For each etiological possibility, both PNEUMON-IA and the experts provided a causal possibility, expressed as a linguistic label (i.e., "almost impossible"). Linguistic labels were then converted to numeric values. In the majority of cases, an etiological diagnosis was unavailable to be used as a gold standard. To overcome this limitation, distances between arrays of etiological possibilities given by specialists and by PNEUMON-IA were considered as an agreement measure between diagnoses. Cluster analysis based on those distances was used to classify PNEUMON-IA among experts. Results showed the same differences between specialists and PNEUMON-IA as among the specialists themselves. The method used to validate PNEUMON-IA could prove useful to assess the performance of expert systems in fields where no gold standard is available.


Plots for examination of univariate twin data.

We discuss informative plots for univariate twin data that can be used in conjunction with twin data analyses. The plots are useful for spotting outliers, spotting possible single gene effects, and displaying the contribution of individual twin pairs to the fit of genetic models of the data. We illustrate the use of the plots on bone mineral data, and present programs for generating the plots in SAS.


Reconstruction of the electrocardiogram during heart surgery.

Electrocardiograms (ECG) recorded during arrhythmia surgery are used for identification of arrhythmias of different morphology. However, the interpretation of an intraoperative ECG is difficult because some leads cannot be recorded and the signals of the remaining leads often differ from those of a preoperative recording because of the sternotomy. Therefore, a method for reconstruction of a complete intraoperative ECG, which resembles a preoperatively recorded ECG, was studied in 24 patients undergoing heart surgery. The reconstruction method involves calculating coefficients for a transformation matrix, using a preoperative ECG recording and a first intraoperative ECG recording. Once this matrix has been established, further intraoperative recordings can be transformed into an ECG which strongly resembles a preoperative ECG. The correlation between reconstructed intraoperative leads and the corresponding preoperative leads was high in the leads Vx and Vy (median correlation coefficient 0.98 and 0.97) and slightly smaller in lead Vz (0.94). Further studies will prove if the method can be useful in arrhythmia surgery.


A parallel implementation of the backward error propagation neural network training algorithm: experiments in event identification.

An artificial neural-network-based (ANN) event detection and alarm generation system has been developed to aid clinicians in the identification of critical events commonly occurring in the anesthesia breathing circuit. To detect breathing circuit problems, the system monitored CO2 gas concentration, gas flow, and airway pressure. Various parameters were extracted from each of these input waveforms and fed into an artificial neural network. To develop truly robust ANNs, investigators are required to train their networks on large training data sets, requiring enormous computing power. We implemented a parallel version of the backward error propagation neural network training algorithm in the widely portable parallel programming language C-Linda. A maximum speedup of 4.06 was obtained with six processors. This speedup represents a reduction in total run-time from 6.4 to 1.5 h. By reducing the total run time of the computation through parallelism, we were able to optimize many of the neural network's initial parameters. We conclude that use of the master-worker model of parallel computation is an excellent method for speeding up the backward error propagation neural network training algorithm.


Evaluation of a computer program for teaching laboratory diagnosis of acid-base disorders.

A computer program was evaluated as a tool for increasing the diagnostic acumen of medical housestaff and students in identifying acid-base disorders. The participants were randomized into two groups; group A (N = 20) was encouraged to use the software, and group B (N = 19) was denied access. Pre- and post-tests were administered to delineate the groups' ability to identify correctly an acid-base disorder from laboratory data (electrolytes and arterial blood gas). During 6 weeks, group A used the computer for a mean of 2.83 h (range 1 to 6). The mean +/- SE number of correct answers out of 20 questions, prior to use of the computer program, were 5.7 +/- 0.8 (95% confidence interval 3.9 to 7.5) for group A and 5.2 +/- 0.6 (95% confidence interval 3.9 to 6.5) for group B. These results were not statistically different. Correct responses increased significantly in group A to 10.3 +/- 0.9 (P < 0.0001, 95% confidence interval 8.4 to 12.2) but did not increase significantly in group B. The data suggest that this software program was effective in increasing the diagnostic capabilities of medical housestaff and students for identifying acid-base disorders.


A neural network architecture for understanding discrete three-dimensional scenes in medical imaging.

Magnetic resonance and computed tomography produce sets of tomograms which are termed discrete 3D scenes. Usually, discrete 3D scenes are analyzed in two dimensions by observing each tomogram on a screen so that the three-dimensional information contained in the scene can be recovered only partially and qualitatively. The three-dimensional reconstruction of the shape of biological structures from discrete 3D scenes would allow a complete and quantitative recovery of the available information, but this task has proved hard for conventional processing techniques. In this paper we present a system architecture based on neural networks for the fully automated segmentation and recognition of structures of interest in discrete 3D scenes. The system includes a retina and two main processing modules, an Attention-Focuser System and a Region-Finder System, which have been implemented by using feed-forward nets trained with the back-propagation algorithm. This architecture has been tested on computer-simulated structures and has been applied to the reconstruction of the spinal cord and the brain from sets of tomograms.


The chronic disease data bank model: a conceptual framework for the computer-based medical record.

The principles underlying the chronic disease data bank model are straight-forward: (1) the purpose of medical care is to improve patient outcomes; (2) patient outcomes in contemporary developed societies are overwhelmingly linked to chronic illnesses and degenerative processes and will become increasingly so; (3) such outcomes have multiple determinants including the psychological and social, as well as the biologic; (4) outcome antecedents (risk factors) may precede clinical illness by years or decades; and (5) these complex characteristics require for their study (a) computer aid and (b) longitudinal data. The chronic disease data bank provides an important resource, available to many investigators, for examination of the complex set of clinical and policy questions arising with long-term illness and addressing the questions of lifetime health. The chronic disease data bank consecutively enrolls eligible subjects, follows them for life, and amasses time-oriented, multidisciplinary data including clinical findings, medical history, demographics, treatments, resource utilization and disease outcomes, and assessing both the quality of life and its duration. Analyses are longitudinal and time-series in type, examining changes in trends and tempo of the disease, and are focused upon long-term outcomes. Outcomes are regularly and carefully assessed, and include the outcome dimensions of death, disability, discomfort, iatrogenic toxicity, and dollar cost. Specific studies address the description of the disease from biologic, demographic, economic, and social viewpoints, identify the factors associated with good and bad outcomes, and assess the effects of treatment, both good and ill. The clinical and policy goals are focused upon delaying transitions from more benign disease states to more serious ones, thus improving both longevity and the quality of life. The time is appropriate to consider generalization of the chronic disease data bank model to the usual clinical care situation, with large rewards in improvement of the quality of care. The traditional medical record lacks systematic documentation of end results and of important covariates related to health risks. As such, it cannot readily be used to assess the ultimate quality of care and to establish a feedback loop to change behaviors and thereby improve outcomes. It is weak where the chronic disease data bank is strong. The technology is transferable.


GOFCOX: a computer program for the goodness-of-fit analysis of the Cox proportional hazards model.

GOFCOX is a user-friendly FORTRAN program for assessing the adequacy of the Cox proportional hazards model. The underlying methodology is based on the comparison of the maximum partial likelihood estimator and a weighted parameter estimator. The latter is the root to an estimation equation that assigns varying weights to the individual contributions to the partial likelihood score function. The weighted and unweighted parameter estimators have the same expectation under the Cox model, but tend to differ when the model is inappropriate. The GOFCOX program computes a rich class of weighted parameter estimators and corresponding goodness-of-fit test statistics. The program runs on both mainframe computers and microcomputers. The running time is minimal even for large data sets. A simple example is provided to illustrate the features of the program.


Computer quantitation of saturation impairment time as an index of oxygenation during sleep.

The measurement of oxygenation during sleep has become a standard procedure in the assessment of hypoxemia in patients with various disorders. However, an accepted method for quantitating this hypoxemia is not available. This study describes the development of computerized data acquisition and analysis programs to quantitate nocturnal hypoxemia in patients with sleep and breathing disorders. The acquisition program samples the voltage output from pulse oximeters used to measure oxyhemoglobin saturation (SpO2) and stores this on an IBM PC or compatible computer. The analysis program integrates the SpO2 over time below the patient's pretest baseline as well as the integral below 90, 80, 70, 60 and 50% saturation. We refer to each integral as Saturation Impairment Time or SIT. In order to compare these integrals between patients or between the same patient but different studies, the integral is divided by the total sleep study time. We refer to each of these integrals, corrected for sleep study time, as the SIT index. Evaluation of the SIT index in 10 consecutive patients referred for various sleep disorders revealed acquisition program detection and deletion of 48 of 57 (86%) oximeter probe artifacts (mean duration of 3 seconds for undetected artifacts). There were no significant artifacts in the analysis program calculation of the SIT index in these same patients. In conclusion, computer programs were developed to measure and quantitate oxygen saturation measured by oximeters. Preliminary results reveal an accuracy of measurement which should prove acceptable in further clinical evaluations.


EMSA: a SAAM service for the estimation of population parameters based on model fits to identically replicated experiments.

This paper presents a new technique for the aggregation of models to produce population parameter estimates based on a set of identically replicated experiments. After describing the theoretical basis for the technique we discuss tactical and strategic issues associated with its implementation in the SAAM software. Finally, we demonstrate its utility in the aggregation of models fitted to four simulated experiments.


Cohen's weighted kappa with Turbo Pascal (FORTRAN).

A microcomputer based Turbo Pascal and FORTRAN program for Cohen's weighted kappa (kappa w) is given. Three clinical applications for kappa w are also presented. A typical data file, the Pascal and FORTRAN program listing and corresponding output are given.


TWINAN90: a FORTRAN program for conducting ANOVA-based and likelihood-based analyses of twin data.

We discuss the program, TWINAN90, which can perform several different types of analysis of twin data. TWINAN90 incorporates the ANOVA-based twin analyses from the TWINAN twin analysis program, and also includes maximum likelihood estimation of parameters from three path models. Another feature of TWINAN90 is the optional output of a pedigree file which can be read by the quantitative genetics package FISHER. The diagnostic features of the program make TWINAN90 useful also for preliminary analyses prior to the use of more sophisticated modeling procedures which are available in packages such as LISREL and FISHER. An annotated printout from TWINAN90 is presented to illustrate the statistical analyses performed in the program.


An integrated system for quantitation of chemotaxis using a 48-well millipore filter assay.

We have established a computerized system for quantification of human neutrophil motility using a 48-well chemotaxis assay. The software is primarily written in the Unix C-shell and is designed to integrate with standard statistical and graphics packages and permit analysis either under Unix or MS-DOS. We demonstrate how simple image analysis techniques may be used to count neutrophils that have traversed a polycarbonate filter. Methods of optical optimization, cell counting and integration with the Statistical Analysis System (SAS) are presented.


CD-ROM source data uploaded to the operating and storage devices of an IBM 3090 mainframe through a PC terminal.

A powerful method of processing MEDLINE and CINAHL source data uploaded to the IBM 3090 mainframe computer through an IBM/PC is described. Data are first downloaded from the CD-ROM's PC devices to floppy disks. These disks then are uploaded to the mainframe computer through an IBM/PC equipped with WordPerfect text editor and computer network connection (SONNGATE). Before downloading, keywords specifying the information to be accessed are typed at the FIND prompt of the CD-ROM station. The resulting abstracts are downloaded into a file called DOWNLOAD.DOC. The floppy disks containing the information are simply carried to an IBM/PC which has a terminal emulation (TELNET) connection to the university-wide computer network (SONNET) at the Ohio State University Academic Computing Services (OSU ACS). The WordPerfect (5.1) processes and saves the text into DOS format. Using the File Transfer Protocol (FTP, 130,000 bytes/s) of SONNET, the entire text containing the information obtained through the MEDLINE and CINAHL search is transferred to the remote mainframe computer for further processing. At this point, abstracts in the specified area are ready for immediate access and multiple retrieval by any PC having network switch or dial-in connection after the USER ID, PASSWORD and ACCOUNT NUMBER are specified by the user. The system provides the user an on-line, very powerful and quick method of searching for words specifying: diseases, agents, experimental methods, animals, authors, and journals in the research area downloaded. The user can also copy the TItles, AUthors and SOurce with optional parts of abstracts into papers under edition. This arrangement serves the special demands of a research laboratory by handling MEDLINE and CINAHL source data resulting after a search is performed with keywords specified for ongoing projects. Since the Ohio State University has a centrally founded mainframe system, the data upload, storage and mainframe operations are free.


Cardiology education using hypermedia and digital imagery.

A computer-based educational system for the study of cardiovascular imaging is described. This system, based on HyperCard * and a standard Macintosh II, integrates hypertext retrieval, computer graphics, sound, and medical images into a single interactive environment stored on a standard hard disk. This 'hypermedia' approach allows arbitrary complexity coupled with direct, immediate, easy traversal of the images and related text, which provides the opportunity for students to move at their own pace, choose their own direction through the material and repeat as often as desired. Storage on magnetic medium allows for easy updating with new studies and material in order to keep pace with advances in medical imaging technology. The system could be mastered onto CD-ROM for ease of distribution if so desired. The system includes a tutorial on the basics of digital image representation and example studies from cineangiography, nuclear medicine, echocardiography and magnetic resonance imaging of the heart. Quantitative techniques for evaluation of left ventricular function are explained using computer graphics overlays on the original medical images. Color encoded functional images are also included as an aid to visualization of ventricular performance data. The system has proven useful as a primer for digital imaging in cardiology prior to specific case study in a traditional mentor relationship.


Influence of thyroid status regulation and Synovex-S implants on growth performance and tissue gain in beef steers.

The separate and combined effects of Synovex-S (SYN) ear implants and thyroxine (T4)-5'-monodeiodinase inhibition (Trial 1) and T3 injection to create a mild elevation in circulating T3 concentrations (Trial 2) on BW gain and composition of gain were studied. Trial 1 used 24, 285-kg Angus steers in two experimental phases. Low-level feeding of propylthiouracil (PTU, 1.5 mg/kg BW daily) was used to achieve inhibition of T4-5'-monodeiodinase activity (TMA). Twelve steers received neither treatment (control) and 12 received SYN+PTU (hypothesized to maximize weight gain) from 0 to 56 d (phase 1) in a single factor treatment comparison. Subsequently, PTU was fed to six control steers and not fed to six of the original SYN+PTU steers from 56 to 175 d (phase 2) in a 2 x 2 arrangement of treatments. Trial 2 used 24, 302-kg Angus-Hereford steers. Treatments were without or with SYN and without or with sc injections of T3 in polyethylene glycol (2 micrograms/kg BW every 48 hr) in a 2 x 2 factorial arrangement of treatments. In both trials, all steers were individually fed a diet of a corn-based concentrate and silage mixture at an equal metabolizable energy intakes per unit of metabolic body weight (.25 Mcal/kg BW.75). Measurements of daily dry matter intakes, weekly BW, 28-d estimates of empty body components (measured by urea dilution), final TMA (trial 1) and plasma thyroid hormone concentrations were obtained. In both trials, SYN increased BW gain and protein accretion.(ABSTRACT TRUNCATED AT 250 WORDS)


Opioid modulation of the hypothalamo-pituitary-adrenal axis in dairy cows.

Plasma cortisol responses to an intravenous bolus treatment with 250 mg naloxone, 300 mg morphine or a combination, were studied in Holstein-Friesian cows; 4 in early lactation (29-43 d postpartum) and 7 in mid-lactation (90-155 d post-partum). Blood samples were collected every 15 min from 60 min before to 90 min after treatment. Naloxone induced an immediate increase in cortisol concentration, reaching a peak within 30 min. The cortisol response (area under the curve) was positively correlated with pre-naloxone cortisol concentrations (r = 0.7, p < 0.05). The mean increase in cortisol concentration after naloxone appeared to be lower in early lactation (1.8 ng/ml) than in mid-lactation (8.3 ng/ml). In contrast, morphine consistently suppressed mean tonic plasma cortisol concentration by 2.7 ng/ml below baseline for at least 90 min. When given with morphine, naloxone counteracted the suppressive effects; the cortisol response was similar to that after naloxone alone. A cow in mid-lactation, suffering from chronic lameness (joint infection), gave opposite results, i.e., treatment with morphine alone increased cortisol concentration, whereas morphine with naloxone did not result in the expected large increase in plasma cortisol concentration. In conclusion, the hypothalamo-pituitary-adrenal axis of dairy cows appears to be under suppressive opioidergic control. However, the opioidergic system involved in hypothalamo-pituitary-adrenal functions of an animal under chronic stress behaved in an opposite manner.


Is nutritional anestrus precipitated by subfunctional corpora lutea in beef cows?

Thirty-four multiparous, lactating, cyclic beef cows which calved in moderate body condition were used to determine effects of restricted nutrition on corpus luteum (CL) development and endocrine status. At 78 d postpartum, six cows were assigned to a control (CON) diet (26.0 Mcal ME), fed to increase bodyweight (BW) and body condition score (BCS), and the remaining 28 cows were fed to lose BW and BCS on a restricted (RES) diet (14.0 Mcal ME). Following a 40-d adjustment period on respective diets, estrous cycles were synchronized and cows bled daily for determination of progesterone (P4), luteinizing hormone (LH) and insulin (INS) beginning at the synchronized estrus. Ultrasonography was used to determine the ovulatory follicle and CL development. Control cows were maintained for one estrous cycle and were ovariectomized on day 11 of their second cycle. Ten cows on restricted diet (RES-C) continued to form a functional CL (P4 > 1.5 ng/ml at day 10 of an estrous cycle) through as many as 5 cycles, after which observations were discontinued. Fourteen cows on restricted diet (RES-A) were ovariectomized on day 11 of a cycle when a CL was identified by ultrasonography, but was subfunctional (P4 < 1.5 ng/ml on day 10 of that cycle). Four additional RES-A cows which had subfunctional CL were not ovariectomized but were bled for an additional 25 d. At ovariectomy, CL and ovarian weights were collected. Luteal tissue was prepared for evaluation of P4 synthesis, LH responsiveness in vitro, and for determination of P4 content and total LH receptors. Bodyweight and BCS increased in CON cows; whereas, RES cows lost BW and BCS (P < .05). In the cycle prior to ovariectomy, serum P4 and LH were not different in 18 RES-A cows which developed subfunctional CL in comparison to CON cows. Four RES-A cows not ovariectomized but bled for an additional 25 d neither exhibited estrus, ovulated, nor had P4 concentrations greater than .3 ng/ml. Serum INS was lower in RES-A cows during the cycle prior to ovariectomy than in CON cows (P < .05). During the 11-d period prior to ovariectomy, mean serum P4 and INS were lower in RES-A cows than in CON cows (P < .05); however, serum LH was not different. Furthermore, CL and ovarian weights, P4 content of CL, secretion of P4 by luteal tissue in response to LH in vitro and LH receptor number were not different between CON and RES-A cows. In conclusion, nutritional anestrus may be preceded by the formation of a CL with lower steroidogenic output in vivo. However, luteal tissue, collected from RES-A cows, did not appear to be subfunctional during in vitro incubation when substrate availability and gonadotropin support were equal between diets.


Effect of age and intake on growth hormone kinetics in dairy heifers.

The effects of aging and intake on growth hormone (GH) kinetics and GH-releasing factor (GRF)-induced GH concentrations were studied in two groups of 12 Holstein heifers each (80 d, 85 kg: young; and 273 d of age, 246 kg: old). Each group was then equally subdivided into full-fed (FF) and restricted-fed (RF) subgroups. After 11 d of intake treatment, animals were infused for 3 hr with GH (1.5 mg/hr) in order to calculate GH metabolic clearance rate (MCR), secretion rate (SR) and half-life (t 1/2). Two d later, total plasma volume was determined and the following day, all heifers received a GRF challenge (5 micrograms/kg i.v.). The following values are LSM +/- SE for young-FF, young-RF, old-FF and old-RF. Rate of secretion was not affected by any treatment, averaging 1.51, 1.25, 1.34, and 1.40 +/- .23 micrograms/min. Aging increased (P < .01) MCR (186, 159, 382, and 300 +/- 21 ml/min) and increased plasma volume (P < .01), which resulted in lower basal GH concentrations. Aging also decreased (P < .01) the area under the GH response curve following GRF injection (AUC: 12442, 21114, 5155, and 6308 +/- 1776 ng.min/ml) but did not affect average GH quantity in the plasma after the GRF challenge. Feed restriction decreased (P < .05) MCR, but not enough to affect basal GH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)


Androgens modulate growth hormone-releasing factor-induced GH release from bovine anterior pituitary cells in static culture.

Static primary cultures of bovine anterior pituitary (AP) cells were utilized to study the effect of sex steroids on basal growth hormone (GH) and GH-releasing hormone (GRF)-stimulated release of GH. The AP cells (5 x 10(5) cells/well) were allowed to attach for 72 hr and become confluent before treatments were imposed. Cells were incubated for an additional 24, 48 or 72 hr with either estradiol-17 beta (E2, 10(-11) to 10(-8) M), testosterone (T, 10(-8) to 10(-5) M), dihydrotestosterone (DHT, 10(-9) to 10(-6) M) or 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol, 10(-11) to 10(-8) M). Media were collected every 24 hr and GH concentrations determined by RIA. Incubation of calf AP cells with gonadal steroids did not affect (P > 0.05) basal GH released at 24, 48, or 72 hr. In another experiment, calf AP cells were incubated with the same concentrations of the steroids for 24 hr, media harvested, cells washed and challenged in serum-free media for 1 hr with bovine GRF 1-44-NH2 (10(-8) M). In non-steroid treated wells, GRF increased (P < 0.05) GH from 58 to 134 ng/ml. Incubation with E2 or 3 alpha-diol did not affect (P > 0.05) GRF-induced GH release; however, preincubation with T (10(-5) M) and DHT (10(-9), 10(-8) and 10(-7) M) increased (P < 0.05) GRF-induced GH release above control concentrations (195, 235, 190 and 185 ng/ml, respectively). At the doses tested, sex steroids did not affect basal release of GH, but androgens increased responsiveness of somatotropes to GRF.


Comparative morphometry and steroidogenic function of antral ovine follicles destined for ovulation or atresia.

An experimental model was established in the ewe allowing one to predict with accuracy an antral follicle that coincidentally would either undergo ovulation (6-8 mm diameter) or atresia (3-4 mm diameter) following synchronization of luteal regression and the onset of the gonadotropin surge. Quantitative morphometric and hormonal criteria were used to make direct comparisons of such follicles collected throughout the preovulatory period. There were progressive alterations in percentages of granulosa cells exhibiting pyknotic nuclei, dispersion of granulosa cells, oocyte maturation, thecal vascular dynamics and extravasation of leukocytes. Nevertheless, no significant variations in temporal patterns were observed between follicular classification. The most notable anatomical distinction between preovulatory and atretogenic follicles was that the former had come into closer contact with the ovarian surface epithelium. The dominant follicle had a higher capacity than the subordinate follicle to produce estradiol before the gonadotropin surge; however, ensuing profiles of steroidogenic function (i.e., shift from the delta 5 to delta 4 pathway) occurred in parallel. Thus, in many respects the follicular mechanics of ovulation and atresia in the sheep appear analogous.


N-methyl-d,l-aspartate stimulates growth hormone and prolactin but inhibits luteinizing hormone secretion in the pig.

The effects of n-methyl-d,l-aspartate (NMA), a neuroexcitatory amino acid agonist, on luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) secretion in gilts treated with ovarian steroids was studied. Mature gilts which had displayed one or more estrous cycles of 18 to 22 d were ovariectomized and assigned to one of three treatments administered i.m.: corn oil vehicle (V; n = 6); 10 micrograms estradiol-17 b/kg BW given 33 hr before NMA (E; n = 6); .85 mg progesterone/kg BW given twice daily for 6 d prior to NMA (P4; n = 6). Blood was collected via jugular cannulae every 15 min for 6 hr. Pigs received 10 mg NMA/kg BW i.v. 2 hr after blood collection began and a combined synthetic [Ala15]-h GH releasing factor (1-29)-NH2 (GRF; 1 micrograms/kg BW) and gonadotropin releasing hormone (GnRH; .2 micrograms/kg BW) challenge given i.v. 3 hr after NMA. NMA did not alter LH secretion in E gilts. However, NMA decreased (P < .02) serum LH concentrations in V and P4 gilts. Serum LH concentrations increased (P < .01) after GnRH in all gilts. NMA did not alter PRL secretion in P4 pigs, but increased (P < .01) serum PRL concentrations in V and E animals. Treatment with NMA increased (P < .01) GH secretion in all animals while the GRF challenge increased (P < .01) serum GH concentrations in all animals except in V treated pigs. NMA increased (P < .05) cortisol secretion in all treatment groups. These results indicate that NMA inhibits LH secretion and is a secretagogue of PRL, GH and cortisol secretion with ovarian steroids modulating the LH and PRL response to NMA.