Heart rate analysis in 24 patients treated with 150 mg amitriptyline per day

Twenty-four patients treated with 150 mg amitriptyline per day for an episode of major depression underwent a standardized heart rate analysis (HRA) before therapy and after 14 days. The battery of cardiovascular reflex tests included the determination of the coefficient of variation (CV) while resting and during deep respiration, a spectral analysis of heart rate, the heart rate response to standing, and the Valsalva manoeuvre. The results of the initial HRA did not differ from a group of 24 normal control subjects matched for age and sex. On day 14 of treatment the patients showed significantly reduced values of heart rate variability in all tests (P<0.0001), probably due to the anticholinergic side effects of amitriptyline. Heart rate increased form 78.1 to 93.6 bpm on average (P<0.0001). Abnormal CV at rest was registered in 96% of the patients; during deep respiration 29% showed abnormal CV results. An abnormal spectral analysis was found in 100% of the cases (low frequency peak: 42%, mid-frequency peak: 100%, high frequency peak: 79%). The heart rate response to standing was abnormal in 75% and the Valsalva test in 33% of the cases. Eighty-eight percent of the patients fulfilled the criteria of a cardiovascular autonomic neuropathy under the conditions of amitriptyline therapy. As yet, the consequences of these changes for the patients have not been sufficiently elucidated.     

Effects of mercury on larval and adult grass shrimp (Palaemonetes pugio)

Tolerance to mercury in two populations of the grass shrimpPalaemonetes pugio was examined at different stages of this animal's life cycle. One population came from a mercury-contaminated creek, Piles Creek (PC), near industrialized Linden, New Jersey. The other population came from a relatively clean area, Big Sheepshead Creek (BSC), near non-industrialized Tuckerton, New Jersey. Larval grass shrimp showed no significant difference between populations in terms of mortality in 0.01 mg/L HgCl₂, although treated BSC larvae metamorphosed significantly (P < 0.05) more slowly than their respective control group. While no BSC larvae survived the 0.0125 mg/L methylmercuric chloride (meHg) treatment, PC larvae exposed to 0.0125 mg/L meHg survived as well as their controls, indicating enhanced tolerance to meHg in this population.Adult shrimp were exposed for 14 days to control, 0.025 mg/L meHg, 0.025 mg/L HgCl₂, 0.05 mg/L meHg, or 0.05 mg/L HgCl₂ PC shrimp were significantly (P < 0.05) more tolerant to both 0.025 mg/L meHg, and 0.025 mg/L HgCl₂ than were the BSC adults.Polyacrylamide gel electrophoresis suggests that both populations of shrimp are capable of producing a metallothionein like protein (MT) in response to treatment with HgCl₂; MT is found in higher levels in field-caught PC shrimp than in field-caught BSC shrimp. MT was not present in field-collected, viable eggs from either population.     

Ganglioglioma: A clinicopathological study of 10 cases

The clinical, radiological, and pathological features in 10 cases of ganglioglioma are described. The clinical data were derived from the patients' medical records, including a review of the age, sex, details of the presenting symptoms, radiological imagings, surgical intervention, and the clinical outcome. Age ranged from 1 to 66 years (mean 29); there were five males and five females. The tumors were located in the fronto-medial, bifrontal, temporal, temporo-basal, temporo-parieto-occipital, and parietal lobes; the 3rd ventricle; the cervicothoracic spinal cord; and the conus medullaris. The presenting symptoms were focal seizures, headaches, hemiparesis, paraparesis, and tetraparesis. In four patients, gross total resection was achieved and in the remaining six patients only subtotal resection was possible. Tumor recurrence occurred in three patients, 1 year, 14 months, and 2 years after the first operation. The histopathologic appearance of gangliogliomas showed a broad variation of the neuronal, glial, and stromal component. Studying proliferation characteristics, labeling for Ki-67 ranged from 0 to 13.7% (mean 4.1) and for PCNA from 0 to 32.1% (mean 20.4). Due to their favorable prognosis, early recognition and correct diagnosis are important in order to avoid progressive neurological deficits and unnecessary aggressive therapy. The application of immunohistochemistry for both neuronal (synaptophysin, NSE, NFP) and astrocytic (GFAP) cell markers, as well as proliferation markers, are recommended in the diagnostic setting for gangliogliomas. The treatment of choice is total surgical resection. The role of radio- and chemotherapy is still controversial.     

Evaluation of gemfibrozil therapy: predictive response from lipoprotein subfraction analysis.

Subjects with high-density lipoprotein cholesterol (HDL-C) values of less than 47 mg/dL (mean 35.6 +/- 5.5 mg/dL) were selected for this study to examine relationships between plasma lipids, lipoprotein components, and the outcome of gemfibrozil therapy. Changes in plasma lipoprotein subfractions were determined to better understand the previously observed variability of the responses in both HDL-C and triglycerides to gemfibrozil. Based on the data collected, an attempt was made to identify pretreatment lipid parameters that may be predictive regarding the efficacy of gemfibrozil therapy. Serum samples were analyzed at the outset and after the conclusion of 12 weeks of gemfibrozil therapy. Because the HDL-C response to therapy was highly variable, the data from patients were separated into two groups, responders (>20% increase in HDL-C) and nonresponders (<20% increase in HDL-C). The lipid components of lipoprotein subfractions were evaluated using multiple regression analysis yielding predictive models that show the relationship between specific lipoprotein subfractions and the percentage change in HDL-C and posttreatment triglyceride levels. Group classification was then predicted with 78% accuracy using specific lipoprotein subfractions to estimate an individual's percentage change in HDL-C. The major difference between the responder and nonresponder groups was their respective correlations between triglyceride-lowering and changes in HDL-C. In the responder group, there was a significant correlation between the changes in HDL-C and the lowering of triglycerides (r = 0.61, p = 0.03), whereas the nonresponder group showed no such correlation (r = 0.17, p = 0.52). The predictive model also proved to be highly accurate in forecasting the effectiveness of the triglyceride-lowering action of gemfibrozil in this group of patients.     

Effects of diflubenzuron on limb regeneration and molting in the fiddler crab, Uca pugilator

Fiddler crabs, Uca pugilator, were exposed to the insect growth regulator diflubenzuron (Dimilin^®) at 0.5, 5, and 50 μg/l after multiple autotomy of one chela and five walking legs. Regeneration of the first walking leg was monitored, and time to ecdysis, mortality, and morphology of the regenerated limbs observed. Continuous exposure to the chemical produced a dose-dependent retardation of regeneration. Animals molting in the higher concentrations exhibited significant mortality at ecdysis. Exposure to the pesticide for a single week produced similar but less severe effects. However, if crabs molted while in the pesticide, significant mortality was observed. The presence of sediment in the container with the crab moderated the effects of the pesticide, but did not eliminate them.

The regenerated limbs of the crabs that survived ecdysis were found to have lesions in the form of black areas in which the cuticle was improperly developed. These lesions were seen in crabs that had been in the pesticide for only one week (week 2 or week 3) as well as those that had had continuous exposure. They were also seen in crabs that regenerated in Dimilin with sediment. In addition, the number of setae on limbs was reduced compared to the number on limbs that had regenerated in clean sea water.     

Adult polyglucosan body myopathy with subclinical peripheral neuropathy: case report and review of diseases associated with polyglucosan body accumulation

A 65-year-old female had polyglucosan body myopathy, usually called "polysaccharide storage myopathy" that presented with increasing distal paresis and only slight weakness of the proximal limb girdle musculature. Muscle biopsy revealed dystrophic changes that could have been mistaken for muscular dystrophy, and the characteristic light as well as electron microscopic features of polyglucosan bodies varying in number at the three sites of muscle biopsies studied (deltoid, quadriceps femoris, and anterior tibial muscle). In addition, there were occasional nonspecific paracristalline mitochondrial inclusions. No abnormal polyglucosan deposits were found in the sural nerve biopsy. Morphometric evaluation of nerve fiber cross sectional areas revealed some degree of demyelination and remyelination, and of nerve fiber degeneration and regeneration. Unlike a series of 10 unselected control sural nerves with Renaut bodies, hypomyelinated nerve fibers were more numerous adjacent to Renaut bodies. This is the first case of polyglucosan body myopathy in which the axon/myelin ratio and the axonal circularity factor in the sural nerve is evaluated and in which a definite lack of polyglucosan bodies or other abnormal glycogen storage products in a peripheral nerve is documented.     

Cytogenetic effects of methylmercury in embryos of the killifish,Fundulus heteroclitus

Fertilized eggs of the killifish,Fundulus heteroclitus, were exposed experimentally to methylmercury (MeHg) to evaluate whether this compound induced cytogenetic effects expressed in the embryos. An additional objective was to assess cytogenetically whetherFundulus embryos from groups that were determined to be more susceptible to the teratogenic effects of MeHg were also more susceptible to its mutagenic effects. Embryos exposed to 0.05 mg/L MeHg for 1 and 7 days post-fertilization were preserved in 10% formalin for cytological examination, while unfixed embryos from the same clutches were evaluated for teratogenic effects. Untreated embyros from each clutch served as controls. Cytogenetic-cytological analyses of fixed treated susceptible embryos that exhibited teratogenic effects revealed decreased mitotic counts (5.0-fold), and increased chromosomal aberrations (2.5-fold) when compared to their controls. There were also decreased mitotic counts (1.5-fold) and increased chromosomal aberrations (2-fold) in embryos from resistant groups when compared to their controls. Exposure to MeHg also retarded development. Forty to fifty percent of the susceptible and resistant control embryos reached the tail-bud stage, but only 28% of the treated resistant and none of the treated susceptible embryos reached this stage. There was also a significant correlation (P < 0.05) between teratogenic and mutagenic effects of MeHg in early stages ofFundulus.     

The controversy about a sexual dimorphism of the human corpus callosum

A sexual dimorphism of the splenium corporis callosi in man was reported in 1982. The authors described the posterior part of the female corpus callosum to be larger and more bulbous than its male counterpart. From the lateralization research, it has previously been stated that the female brain is less well lateralized for visuospatial functions than the male. The authors postulated that a larger splenium implies a larger number of fibers and that the number of interhemispheric fibers correlates inversely with lateralization of function. However, their sample was very small and not adequately matched for sex. Therefore, we reinvestigated this question. A standardized computer assisted program will be presented. With this program the "classical" parameters have been evaluated and the "rotatory diameter measurement" was performed. No differences between the sexes were seen either for the splenium corporis callosi or for the other parts of the corpus callosum.     

Primary cerebral lymphoma with glomerular renal involvement

We report a case of primary cerebral lymphoma metastasizing to the kidney with exclusive involvement of the glomeruli. We discuss the possible explanations of this unusual phenomenon, and present some of the unusual clinical features of the case. Nephropathologists interpreting glomerular hypercellularity should always consider metastatic neoplasms as a possible, though rare, cause.     

The kyphoscoliotic type of Ehlers-Danlos syndrome (type VI): differential effects on the hydroxylation of lysine in collagens I and II revealed by analysis of cross-linked telopeptides from urine

The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS type VIA) (OMIM 225400) is an autosomal recessive connective tissue disorder that results from mutations in the lysyl hydroxylase 1 gene (PLOD1) causing underhydroxylation of lysine residues in tissue collagens, particularly of skin. Previous studies have shown that the pool of collagen cross-linking amino acids, hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP) excreted in urine has an abnormally low HP/LP ratio, which is diagnostic of the condition. Here we isolated cross-linked peptides containing these residues from the urine of a child with EDS VIA homozygous for a mutation that results in a stop codon and effective null expression of PLOD1 enzyme activity. Peptides that had originated from bone type I collagen and cartilage type II collagen were identified. A cross-linked N-telopeptide fraction that is derived from bone type I collagen contained only LP, no HP, which means that the helical lysines at residues 930 of alpha 1(I) and 933 of alpha 2(I) of the collagen triple-helix had not been hydroxylated. The equivalent peptide fraction from a normal child's urine gave a ratio of HP to LP of 1.5:1 typical for normal bone collagen. A second cross-linked peptide that is derived from the C-telopeptide domain of cartilage type II collagen showed both HP and LP in a 2:1 ratio, compared with 18:1 for the equivalent peptide from a normal child's urine. The results show that in EDS VIA, bone type I collagen is more markedly underhydroxylated than cartilage type II collagen, at least at those helical sites that form cross-links. The residual fraction of HP found in the urine of EDS VI patients therefore appears to be contributed in significant part by the degradation products of cartilage. Since PLOD1 is null, other PLOD genes must be responsible for the helical hydroxylation activity that results in HP. The presented approach of analyzing urinary cross-linked C-telopeptide fragments of type II collagen may allow the detection of chondrodysplasias due to genetic defects in lysyl hydroxylase isoforms active in cartilage.