Anti-adrenal medullary antibodies in IDDM subjects and subjects at high risk of developing IDDM

Previous reports have noted the presence of anti-adrenomedullary antibodies in subjects with insulin-dependent diabetes mellitus (IDDM). We initiated a study to evaluate the presence of complement-fixing anti-adrenomedullary antibodies (CF-ADM) in the following subjects: group 1 (age 4-60 yr), anti-islet cell antibody-positive (ICA+) subjects at high risk of developing diabetes, in which 9 (32%) of 28 were positive for CF-ADM; group 2 (age 6-41 yr), anti-ICA negative (ICA-) subjects at high risk of developing diabetes, in which 0 (0%) of 15 were positive for CF-ADM; group 3 (age 1-58 yr), ICA+ diabetic subjects, in which 7 (30%) of 23 were positive for CF-ADM; group 4 (age 5-68 yr), ICA- diabetic subjects, in which 1 (4%) of 24 was positive for CF-ADM; group 5 (age 20-56 yr), volunteer blood bank donor controls, in which 2 (6%) of 32 were positive for CF-ADM; and group 6, known healthy controls, in which 0 (0%) of 14 were positive for CF-ADM. CF-ADM were increased in group 1 compared with group 2 (P less than .02) and both control groups (P less than .02). CF-ADM were increased in group 3 compared with group 4 (P less than .03) and both control groups (P less than .03 vs. group 5, P less than .05 vs. group 6). Presence of CF-ADM was associated with presence of ICA in group 1 (P less than .02) and group 3 (P less than .03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-sympathetic ganglia antibodies and postural blood pressure in IDDM subjects of varying duration and patients at high risk of developing IDDM

We examined the sera of 94 subjects with insulin-dependent diabetes mellitus (IDDM) for the presence of complement-fixing sympathetic ganglia (CF-SG) antibodies. In a cross-sectional analysis (duration 0-43 yr), 22% had detectable CF-SG antibodies. Subjects at high risk for IDDM were also studied. Four groups were studied: group 1 (aged 4-64 yr) islet cell antibody-positive (ICA+) prediabetic subjects, 10 of 19 (53%) were CF-SG+; group 2 (aged 6-14 yr) ICA- prediabetic subjects (first-degree relatives of IDDM subjects with either transient hyperglycemia, impaired oral glucose tolerance, and/or first-phase insulin release after intravenous glucose tolerance testing), 4 of 9 (44%) were CF-SG+ (2 of the 4 ICA- CF-SG+ subjects have progressed to IDDM); group 3 (aged 1.5-43 yr) ICA+ IDDM subjects (less than or equal to 1 yr duration) 6 of 10 (60%) were CF-SG+; and group 4 (aged 8-59 yr) ICA- IDDM subjects (less than or equal to 1 yr duration), 2 of 11 (18%) were CF-SG+. All groups had increased CF-SG compared with controls. Postural blood pressure and simultaneous CF-SG antibody measurements were performed in 28 IDDM subjects. The drop in systolic blood pressure was greater in the CF-SG+ subjects (P less than .05), and the frequency of CF-SG was greater in the mean to -2SD group (P less than .03) when data were analyzed within mean +/- 2SD of the normal blood pressure response.     

Intravaginal vibrator of long duration.

Intravaginal foreign bodies of long duration are a rare entity and are seen in the practice of Obstetrics and Gynaecology, but patients may present to the Accident and Emergency department for their removal. Various bizarre objects have been inserted into the vagina and many patients are too embarrassed and will wait and try to remove them themselves rather than seek medical advice. Vaginal foreign bodies of long duration may be complicated by fistulas and such patients should be referred to the gynaecologist.     

Peripheral long lines in cystic fibrosis

Improved cannula survival with peripheral long lines has been reported for patients requiring multiple courses of intravenous (i.v.) antibiotics, allowing a more normal and mobile pattern of life (1, 2).
Since June 1992 we have used both the neonatal silastic long line (Epicutaneo‐cava‐catheter, Vygon, Aachen) and the Landmark catheter (Menlo Care, California) for administration of i.v. antibiotics to our cystic fibrosis (CF) patients. Information was collected prospectively on the performance of both types of cannulae over 18 months. Cannula survival time was the same and longer than with conventional short cannulae (1, 3). Patient preference for the neonatal line and a trend towards more phlebitis with the Landmark catheter resulted in the selection of the neonatal line for routine use.     

Adrenal medullary autograft transplantation into the striatum of patients with Parkinson's disease

In eight patients with advanced Parkinson's disease, we performed autograft transplantation of adrenal medulla to the head of the caudate nucleus. Our technique was similar to that developed by Madrazo and co-workers in Mexico City. No major perioperative complications occurred except for somnolence in one patient for 8 days postoperatively. The follow-up period has been at least 6 months in seven of the patients, and only limited benefit has been apparent. The early morning Parkinson examination score in the "off" (unmedicated) state was significantly improved in one patient and slightly better in the other six. Diary card entries suggested a mild trend toward improvement (not statistically significant). Four of the seven patients were taking less levodopa 6 months after the operation than they had been preoperatively; three of five patients were no longer taking dopamine agonists postoperatively. We cannot exclude a placebo effect contributing to any of this improvement. A reduction in medication-induced dyskinesia was also noted, but this result may have been due to adjustments in doses or a slightly less potent effect of medication (or both factors). In summary, we have not yet been able to replicate the dramatic success reported for adrenal medullary transplantation by Madrazo's group, although our patients may have experienced mild to moderate improvement. We continue to maintain follow-up surveillance of these patients.     

Efficacy of transesophageal defibrillation in ventricular fibrillation of long duration

Introduction

Increasing duration of ventricular fibrillation (VF) is associated with a higher risk of ineffective resuscitation. In addition, precountershock chest compression can influence defibrillation success. Transesophageal defibrillation may increase defibrillation success because of the proximity of the esophagus to the heart. We evaluated the efficacy of transesophageal defibrillation compared with standard transthoracic defibrillation after long episodes of VF.

Methods

Defibrillation success after 10 minutes of untreated VF was evaluated in 12 sheep randomized into 2 groups: (group A) in 6 sheep, up to 3 transthoracic shocks were applied, followed by up to 3 transesophageal shocks (first shock: 150 J, second and third shocks: 200 J). (group B) In 6 sheep, 2 minutes of precountershock chest compression preceded the defibrillation shocks. Truncated biphasic shocks were delivered between a sternal and an apical patch electrode for transthoracic defibrillation and between an esophageal and a cutaneous patch electrode for transesophageal defibrillation.

Results

In group A with no precountershock chest compression, external defibrillation failed despite shocks with maximum energy (200 J) in all 6 sheep. Transesophageal defibrillation was successful in 3 sheep (50%). In group B with precountershock chest compression, external defibrillation failed in all 6 sheep. Transesophageal defibrillation was successful with the first shock in all 6 sheep.

Conclusions

Transesophageal defibrillation may terminate VF of long duration that is refractory to standard defibrillation. Precountershock chest compression may increase transesophageal defibrillation success.     

The history and role of long duration stimulation in fMRI

During the past 20 years, BOLD fMRI has developed towards a central and fundamental tool in neuroscience. It has been shown that the BOLD response provides an indicator of neuronal activity in the brain. Consequently, for an accurate interpretation of findings in BOLD MRI experiments and to draw meaningful conclusions about the temporal evolution of neural events, a deep understanding of the nature of the BOLD contrast has become of essential importance. Since the dynamics of the major direct determinants of the BOLD signal (CBF, CBV and CMRO(2)) range between seconds and minutes, long duration stimulation was an early key strategy needed to study and understand the BOLD characteristics. This paper summarizes and discusses the thoughts and rationales of the long duration stimulation studies.     

Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.     

Cosinor analysis for temperature time series data of long duration

The application of cosinor models to long time series requires special attention. With increasing length of the time series, the presence of noise and drifts in rhythm parameters from cycle to cycle lead to rapid deterioration of cosinor models. The sensitivity of amplitude and model-fit to the data length is demonstrated for body temperature data from ambulatory menstrual cycling and menopausal women and from ambulatory male swine. It follows that amplitude comparisons between studies cannot be made independent of consideration of the data length. Cosinor analysis may be carried out on serial-sections of the series for improved model-fit and for tracking changes in rhythm parameters. Noise and drift reduction can also be achieved by folding the series onto a single cycle, which leads to substantial gains in the model-fit but lowers the amplitude. Central values of model parameters are negligibly changed by consideration of the autoregressive nature of residuals.     

Adaptation of human skeletal muscle to endurance training of long duration

Summary. The aim of this study was to examine the adaptive response of skeletal muscle to dynamic training of long duration and low intensity. The response of m. triceps brachii, (TB) and m. quadriceps femoris, vastus lateralis (VL) to training of long duration at an intensity corresponding to approximately 45% of V?O₂, max, has been studied in six subjects. Muscle specimens were taken during training (18.5 miles (30 km)), which involved skiing with a backpack, (6 daydweek, 8 weeks), as well as during a subsequent period of detraining (33 weeks). Increases in oxidative enzyme activities and capillarization during training were limited to the TB. There were parallel increases in citrate synthase (CS) and malate dehydrogenase (MDH) during the first 3 weeks of training (30%). CS then continued to rise (to 90% above pretraining level), while the increase in MDH levelled off. The activity of 3–hydroxyacyl-CoA-dehydrogenase (HAD) and the number of capillaries per fibre increased by 50 % and 40 % respectively. A selective decrease (12%) in area of fibre type IIA was noted during training after a 2-week period of energy deficiency. During the first 6 weeks of detraining, the decrease in CS and HAD (30%) was greater than the decrease in capillaries per fibre (14%). It is concluded that prolonged duration of training is not, in itself, sufficient to elicit an adaptive response in the leg muscles, while a modest training effect was seen for the arm muscles. The finding emphasizes the importance of adequate intensity in physical training programmes.     

Adrenal medullary transplantation into the brain for treatment of Parkinson's disease: clinical outcome and neurochemical studies

Transplantation of adrenal medulla into the caudate nucleus as treatment for Parkinson's disease was performed in eight patients. Although our previous 6-month follow-up revealed early modest improvement, an extension of that follow-up to 1 year disclosed no additional gains in any patient. At the end of 1 year, only one patient could be categorized as moderately improved; three patients were mildly improved, and four patients were unimproved. The rationale for transplanting adrenal medulla was to reestablish a physiologic source of dopamine to the striatum. We measured cerebrospinal fluid (CSF) and plasma catecholamines and metabolites before and after transplantation. Conjugated dopamine (the predominant form of dopamine found in the CSF) and homovanillic acid (the major dopamine metabolite) were modestly and inconsistently increased in the CSF. Conjugated and free epinephrine and norepinephrine, as well as 3-methoxy-4-hydroxyphenylglycol concentrations were not increased in CSF after graft placement, an indication that the adrenal chromaffin cells were no longer producing high levels of these nondopamine catecholamines and metabolites. CSF cortisol concentrations were not increased after transplantation, compared with values from controls, consistent with low numbers of functioning adrenal cortical cells contaminating the graft (or poor survival). Posttransplantation CSF did not induce a neurotrophic effect in cell cultures of 15-day embryonic rat dorsal root ganglion or PC12 (rat pheochromocytoma) cell lines. Survival of samples of patients' adrenal medullary tissue for 2 weeks in tissue culture attested to the viability of the graft at the time of transplantation. The relative concentrations of dopamine to epinephrine or norepinephrine increased in these cultured adrenal medullary cells, presumably because of loss of the glucocorticoid influence on catecholamine synthesis. A wide variety of factors could have contributed to our failure to replicate the earlier impressive results of adrenal-to-brain transplantation reported by others. Continued transplantation studies in animal models of parkinsonism are necessary for better elucidation of these factors.