Flashlamp-excited dye laser therapy of idiopathic vulvodynia is safe and efficacious

Objective: The management of chronic vulvovaginal pain, not explicable on specific histologic grounds, presents a major problem in referral centers for lower genital tract diseases.Study design: This article reports on a two-step protocol in a sample of 175 medical nonresponders, drawn from a 2-year cohort of 725 women with vulvovaginal pain. The first maneuver was the use of a flashlamp-excited dye laser to selectively photocoagulate symptomatic subepithelial blood vessels in 168 women; the second was the microsurgical removal of chronically painful Bartholin's glands in 52 women not responsive or not suited to flashlamp-excited dye laser photothermolysis.Results: Dye laser response rates werer independent of whether patients manifested macroscopic focl of painful erythema (“vestibular adenitis”) or just colposcopically apparent hyperemia-ectasia of the individual blood vessels (“pruritic papillomatosis”) (55% vs 45% after a single surgical procedure; 76% vs 65% after serial retreatment; p not significant). Conversely, response rates were much lower among women in whom pressure on the Bartholin's glands produced sharp, lancinating pain (15% vs 66% after a single surgical procedure; 22% vs 93% after serial retreatment; p < 0.001). Forty-two (85%) of 50 patients with flashlamp-excited dye laser failure had deep pain; however, the impasse to progress was broken by gland removal. Final response rates were 92.5% (complete response 62%; partial response 30%) in the “surface-only” group and 80.3% in the “surface-plus-deep” group (χ² = 14.9; p < 0.001). The major complication was acute bacterial cellulitis, occurring in the first postoperative week. Modification of the treatment protocol to include topical antibiotics with an occlusive dressing reduced the cellulitis rate from 17.2% to 2.5%. In four women (1.8%) Koebner-like exophytic condylomas also developed within 1 month of flashlamp-excited dye laser surgery.Conclusion: The availability of a safe, efficacious, and relatively noninvasive treatment should reduce the need for resective surgery in most patients with idiopathic vulvodynia. 1995; 172; 1684–1701.)     

Duodenal perforation associated with tolazoline.

A neonate, managed with tolazoline for pulmonary hypertension after repair of a congenital diaphragmatic hernia, developed a duodenal perforation. The role of tolazoline in this condition is discussed, and possible measures to reduce its gastrointestinal side effects are proposed.     

Corpus callosum abnormalities in psychopathic antisocial individuals

CONTEXT: Psychopathic antisocial individuals have previously been characterized by abnormal interhemispheric processing and callosal functioning, but there have been no studies on the structural characteristics of the corpus callosum in this group. OBJECTIVES: To assess whether (1) psychopathic individuals with antisocial personality disorder show structural and functional impairments in the corpus callosum, (2) group differences are mirrored by correlations between dimensional measures of callosal structure and psychopathy, (3) callosal abnormalities are associated with affective deficits, and (4) callosal abnormalities are independent of psychosocial deficits. DESIGN: Case-control study. SETTING: Community sample. PARTICIPANTS: Fifteen men with antisocial personality disorder and high psychopathy scores and 25 matched controls, all from a larger sample of 83 community volunteers. MAIN OUTCOME MEASURES: Structural magnetic resonance imaging measures of the corpus callosum (volume estimate of callosal white matter, thickness, length, and genu and splenium area), functional callosal measures (2 divided visual field tasks), electrodermal and cardiovascular activity during a social stressor, personality measures of affective and interpersonal deficits, and verbal and spatial ability. RESULTS: Psychopathic antisocial individuals compared with controls showed a 22.6% increase in estimated callosal white matter volume (P<.001), a 6.9% increase in callosal length (P =.002), a 15.3% reduction in callosal thickness (P =.04), and increased functional interhemispheric connectivity (P =.02). Correlational analyses in the larger unselected sample confirmed the association between antisocial personality and callosal structural abnormalities. Larger callosal volumes were associated with affective and interpersonal deficits, low autonomic stress reactivity, and low spatial ability. Callosal abnormalities were independent of psychosocial deficits. CONCLUSIONS: Corpus callosum abnormalities in psychopathic antisocial individuals may reflect atypical neurodevelopmental processes involving an arrest of early axonal pruning or increased white matter myelination. These findings may help explain affective deficits and previous findings of abnormal interhemispheric transfer in psychopathic individuals.     

Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis

Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity.     

CHROMOSOME 3 MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

Glioblastoma multiforme (GBM), the most malignant type of glioma, is the most common primary brainneoplasm. Although comprehensive therapeutic measures are applied, the prognosis of GBM remains dismal with a median post-treatment survival of less than one year.Modern molecular genetics has demonstrated thatabnormal alterations of tumor suppressor genes (TSGs) and oncogenes are the major mechanisms responsible for the initiation and progression of this malignant tumor.Identifying of related…     

Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro

Recombinant human tumor necrosis factor (rhTNF) has been tested for its effect on myelinated cultures of mouse spinal cord tissue. As controls, recombinant human interferon gamma (rhIFN) and interleukin-2 (rhIL-2) were tested, as well as T-cell supernatants, antigalactocerebroside serum, and normal culture medium. It was found that rhTNF induced delayed-onset (18-24 hr) oligodendrocyte necrosis and a type of myelin dilatation peculiar to this system. Some nerve fibers progressed to demyelination by 72 hours. The myelin dilatation was not reversible by return to normal feeding solution for 3 days. In contrast, rhIFN, rhIL-2, T-cell supernatants, and normal medium had little or no effect on cultures. This mechanism differs from other immune-mediated mechanisms in that it appears that a physiological (not structural) demyelination occurs initially without overt destruction of the myelin sheath. These observations are relevant to the evolution of the multiple sclerosis plaque: dysfunction of ionic channels might contribute to the eventual demise of oligodendrocytes and axons in the longstanding lesion.     

On the development of CNS lesions in natural canine distemper encephalomyelitis

Acute lesions within spinal cord white matter have been studied by light and electron microscopy in 3 dogs suffering from the acute form of canine distemper encephalomyelitis (CDE). Prominent features of these lesions were viral inclusions, giant cell formation, cellular degeneration, myelin breakdown and phagocytic activity by cells believed to be derived from local glia. The viral inclusions occurred in giant cells, many astrocytes, macrophages and occasional oligodendroglia. Only suggestions of active viral replication from cell membranes were present. On the basis of the above features, these CDE lesions were classed as being acute. Perivascular inflammation and parenchymal invasion by haematogenous cells were lacking. However, older, gliotic, demyelinated lesions were always associated with inflammation. The pattern of demyelination in acute CDE lesions differed from those seen in other conditions, in particular the autoimmune demyelinating diseases. In acute CDE lesions, individual fibres became separated from others by rings of cells, the processes of which systematically stripped the myelin from the outer layers of the sheath inwards until a naked segment of axon remained. Some of the macrophages were recognisable as astroglia. Elsewhere, unequivocal astrocytes containing myelin debris were common. The results suggest that inflammation in acute CDE lesions is not a primary event, and that viral invasion causes breakdown of tissue which is accompanied pari passu by myelin destruction. The latter might be related to the non-specific release of host factors (viz. hydrolytic enzymes) or humoral factors during the cellular degeneration. Local cells appeared to participate in the process of myelin phagocytosis. Overt inflammation and damage by haematogenous cells were features only of chronic lesions and have been described previously in studies on chronic CDE lesions. The results are interpreted in terms of their relevance to the study of human subacute sclerosing panencephalitis, of which CDE is considered the animal analogue, and multiple sclerosis, the paradigm of the human demyelinating diseases.     

The effects of prolonged beta-adrenoceptor blockade on heart weight and cardiac intracellular potentials in rabbits.

Estimates were made in vivo in rabbits of the relative beta-receptor blocking potency and duration of action of propranolol and practolol. In further experiments groups of litter mates were injected twice daily with approximately equi-active amounts of propranolol or practolol, or with saline, for several weeks. The heart weights of the treated animals were significantly lower than those of the controls, the water contents were higher, and the dry weight differences were highly significant; -16.8% after 2 mg/kg bd propranolol for six weeks and -33.8% after 10 mg/kg practolol. (The treated animals grew less rapidly than the controls; when corrected for body weight these figures were -11.9% and -20.4%, respectively.) In the practolol group, but not the propranolol group, the duration of the atrial intracellular potentials was prolonged. There was no evidence that the prolonged treatment with either drug had a negative inotropic effect, or reduced positive inotropic responses to isoprenaline.     

Myelin basic protein and myelin-associated glycoprotein in chronic, relapsing experimental allergic encephalomyelitis

One-micron plastic sections of spinal cords from SJL/J mice with chronic relapsing experimental allergic encephalomyelitis (EAE) were reacted immunocytochemically with antiserum to myelin basic protein and myelin-associated glycoprotein. The distribution of myelin basic protein and myelin-associated glycoprotein in myelin sheaths was compared in acute and chronic areas of demyelination. No difference in the size of the lesion was seen with the two antisera. Myelin-associated glycoprotein was seen periaxonally in both normal myelin sheaths and sheaths which showed extensive splitting and ballooning as seen with toluidine blue stain and myelin basic protein antiserum. At least at the level of the light microscope, myelin basic protein antiserum gave intense staining of myelin while antiserum to myelin-associated glycoprotein showed little or no affinity to stain the myelin sheath itself, in contrast to other recent electron microscope observations. A few myelin basic protein or myelin-associated glycoprotein-containing oligodendrocytes were seen in lesion areas and remyelination by oligodendrocytes was rare. These observations are in agreement with findings from other models of EAE and multiple sclerosis where a primary loss of myelin has been implicated.