Results of long-term leukocyte interferon (alpha IFN) therapy using an individually determined dose schedule in recurrent laryngeal papillomatosis

Out of 24 patients with laryngeal papillomatosis 6 (5 female, 1 male) suffered from repeated relapses and underwent long-term treatment with alpha-IFN-therapy. Age at onset of the disease: 1 5/12-16 2/12 years. Duration of illness: 1-7 years, with several relapses were treated surgically and with laser-coagulation. Three out of 6 patients had a tracheal cannula and were cauterized by podophylline at 2-4 week intervals. IFN was given in dosages of 5-20 X 10(4) U/kg 2 or 3 times a week. IFN-dosage for each patient was determined using the induction kinetics of (2'-5')-oligo(A)synthetase (OAS) in the mononuclear cells of the circulating blood of patients with laryngeal papillomatosis. A continuous effect could be achieved by the dose of IFN determined in the described way always before OAS activity decreased to its initial level. All 6 patients responded favorably to the alpha-IFN-therapy. Two patients treated only with IFN showed remission without relapses. In 2 cases IFN was successfully used to prevent relapses after surgical treatment and laser-coagulation. In 2 patients with papillomatosis extending into the main bronchi the disease could only be brought to a standstill, i.e. it was not necessary to remove the papillomas. Two out of 3 patients with laryngeal papillomatosis could be decannulated. Long-term therapy following the above described principles is efficient and without significant side-effects. Three patients are in treatment for more than 3 10/12 years.     

Differential effects of scopolamine on nocturnal cortisol secretion, sleep architecture, and REM latency in normal volunteers: relation to sleep and cortisol abnormalities in depression

Scopolamine (SCOP) (3.0 mu/kg and 6.0 micrograms/kg) and saline were administered intramuscularly at 11:00 PM to eight normal male volunteers in a randomized design, and the effects on the sleep electroencephalogram (EEG) and nocturnal cortisol secretion (via blood sampling every 15 min) were evaluated. Compared to saline, SCOP produced a significant dose-related delay in rapid eye movement (REM) latency. In contrast, neither dose of SCOP significantly affected nocturnal plasma cortisol concentrations. These results suggest that the central cholinergic system that regulates the onset of REM sleep is more sensitive to dysregulation than the cholinergic system that controls the degree of nocturnal cortisol secretion. If central cholinergic overactivity is responsible for both the REM sleep latency and cortisol abnormalities in depressed patients, then our findings with SCOP might help explain why the incidences of these abnormalities are different.     

Evidence for a distinct nigropallidal dopaminergic projection in the squirrel monkey

Injections of the retrograde fluorescent tracer fast blue in the striatum (STR) and nuclear yellow in the internal segment of the globus pallidus (GPi) in the squirrel monkey (Saimiri sciureus) revealed a nigropallidal projection whose cellular origin was largely distinct from that of the nigrostriatal pathway. Neurons containing the tracer injected in GPi were scattered throughout the substantia nigra-ventral tegmental area complex where they formed approximately 20-25% of the total number of retrogradely labeled cells. Only about 5-10% of all positive neurons were double-labeled after STR-GPi injections. In experiments combining the use of the fluorescent tracer propidium iodide with immunofluorescence, the majority of neurons projecting to GPi displayed tyrosine hydroxylase immunoreactivity. Hence, in addition to their important role at striatal level, midbrain dopaminergic neurons may influence directly the output neurons of the basal ganglia at pallidal level in primates.     

Cytoplasmic loop of beta-adrenergic receptors: synaptic and intracellular localization and relation to catecholaminergic neurons in the nuclei of the solitary tracts

Pharmacological studies suggest that beta-adrenergic receptors (beta AR) in the medial nuclei of the solitary tracts (m-NTS) facilitate presynaptic release of catecholamines and also function at postsynaptic sites. We have localized the antigenic sites for a monoclonal antibody against a peptide corresponding to amino acids 226-239 of beta AR in the m-NTS of rat brain. By light microscopy, immunoperoxidase labeling for this antibody was detected in somata and proximal processes of many small cells that were distributed throughout the rostrocaudal extent of the m-NTS. Electron microscopy confirmed the cytoplasmic localization of beta AR in perikarya and proximal dendrites of neurons. Immunoreactivity occurred as discrete patches associated with cytoplasmic surfaces of plasma membrane and with irregularly-shaped saccules with clear lumen in the immediate vicinity. Select regions of nuclear envelopes, mitochondrial membranes, and rough endoplasmic reticulum were also immunoreactive along their cytoplasmic surfaces. In contrast, the Golgi apparatus was labeled, but infrequently. Immunoreactivity was also detected at numerous post- and occasional presynaptic membrane specializations of select axodendritic junctions. Dual labeling for the beta AR-antibody by the immunoperoxidase method and for a rabbit antiserum against the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), by the immunoautoradiographic method within the same sections, further established the precise cellular relations between beta AR and catecholaminergic neurons. Immunoreactivity for beta AR was detected in numerous perikarya and proximal dendrites that did not show detectable levels of TH. However, a few cells were dually labeled for both antigens, as seen by both light and electron microscopy. The TH-labeled terminals formed synapses at junctions both with and without beta AR-like immunoreactivity. These results from the single and dual labeling studies: (1) confirm biochemical predictions that amino acids 226-239 of beta AR protein reside intracellularly; (2) provide the first ultrastructural evidence for beta AR localization within both pre- and postsynaptic membrane specializations of a subset of catecholaminergic synapses; and (3) suggest select intracellular sites that may be involved with synthesis and/or internalization and degradation of the receptor protein.     

Heart size and function of soldiers, athletes, and sedentary men

This study compares the heart sizes and left ventricular masses of soldiers (n = 11) with age- and body size-matched groups of sedentary men (n = 10) and accomplished athletes (n = 11). Echocardiography revealed that active duty soldiers (A) who met minimal fitness standards and pentathletes (P) had greater average left ventricular (LV) end-diastolic volumes (A = 10%, NS; P = 28%, p less than 0.05), stroke volumes (A = 29%, NS; P = 44%, p less than 0.01), and LV masses (A = 22%, NS; P = 76%, p less than 0.01) than sedentary subjects. Athletes had an average LV wall thickness which was 23% (p less than 0.05) greater than that of soldiers and 32% (p less than 0.01) greater than that of sedentary men. The LV wall thickness to radius ratio (h/r) was similar between soldiers and sedentary men, but in athletes the h/r was greater (p less than 0.01) than in the less conditioned subjects. These data suggest that soldiers who meet minimal standards of fitness exhibit cardiac morphometric features consistent with endurance conditioning. However, the soldiers studied were significantly less (p less than 0.001) conditioned than the competitive athletes. These data suggest that improvements in aerobic and cardiac conditioning could be achieved through a greater emphasis on physical training.