Transneuronal transport of herpes simplex virus from the cervical vagus to brain neurons with axonal inputs to central vagal sensory nuclei in the rat.

The recent introduction of live viruses as intra-axonal tracing agents has raised questions concerning which central neurons are transneuronally labelled after application of the virus to peripheral organs or peripheral nerves. Since the central connections of the vagus nerve have been well described using conventional neuronal tracing agents, we chose to inject Herpes Simplex Virus Type 1 into the cervical vagus of the rat. After survival times of up to 3 days the rat brains were processed immunohistochemically using a polyclonal antiserum against herpes simplex virus. Two days after injection of the virus we observed viral antigen in the area postrema and in the nucleus tractus solitarius and the dorsal motor nucleus of the vagus (dorsal vagal complex), principally ipsilaterally. At this survival time the viral antigen in the dorsal vagal complex was largely confined to glial cells. After 3 days the viral antigen was localized both in glia and in nerve cells within the dorsal vagal complex and in brain regions previously demonstrated, using conventional tracing procedures, to contain neurons with axonal projections to the dorsal vagal complex. This was true for medullary, pontine, midbrain and hypothalamic regions and for telencephalic regions including the amygdala, the bed nucleus of the stria terminalis, and the insular and medial frontal cortices. Many of the nerve cells containing viral antigen were displayed in a Golgi-like manner, with excellent visualization of the dendritic tree. Axonal processes, in contrast, were not visualized. We used co-localization studies to confirm previous findings concerning monoamine neurotransmitter-related antigens present in medullary and pontine neurons projecting to the dorsal vagal complex. After 3 days there were many Herpes Simplex Virus Type 1-containing glial cells along the intra-medullary course of the vagal rootlets. However, no viral antigen was found in brain regions containing neurons whose axons pass through the region of glial cell-labelled rootlets. Glial cells containing viral antigen were particularly numerous in brain regions known to receive an input from neurons in the area postrema and the dorsal vagal complex. Taken together with our observation concerning the early appearance of viral antigen within glial cells in the dorsal vagal complex, this suggests that when the virus reaches the axon terminal portion it is transferred to nearby glial cells and possibly enters central neurons by way of these structures.     

Echinomycin (NSC 526417) in recurrent and metastatic nonsquamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group.

Eighteen evaluable patients with recurrent or metastatic nonsquamous carcinoma of the uterine cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. Seven patients had received prior chemotherapy. There was one complete response (5.6%), 95% confidence interval for response of 0-27%. The major toxicity was nausea and vomiting, which was moderate to severe in eight patients. Myelosuppression was minimal. Echinomycin in this dose and schedule displays minimal activity in patients with advanced nonsquamous carcinoma of the cervix.     

Cell groups in the lower brain stem of the rabbit projecting to the spinal cord, with special reference to catecholamine-containing neurons

Two groups of experiments were carried out in rabbits. In the first groups, the distribution of cell bodies within the pons and medulla projecting ipsilaterally and contralaterally to the thoracic or lumbar spinal cord was studied using the horseradish peroxidase (HRP)/tetramethylbenzidine (TMB) procedure. In the second group, both a previously described double-labeling technique and a new modification of it were used to determine the location of catecholamine (CA)-fluorescent pontomedullary cells projecting to the spinal cord. The results demonstrate that the catecholamine (probably norepinephrine)-containing neurons which innervate the thoracic spinal cord are confirmed almost exclusively to the pons where they were found within the A5, A7 and subcoeruleus groups, as well as the ventral portion of the principal part of the locus coeruleus and the more caudal locus coeruleus, including the A4 cell group. Within the medulla oblongata no doubly labeled A2 cells were observed and the few double labeled A1 cells which were observed were confined to the rostral portion of this group. A dense group of HRP-positive but non-fluorescent cells was found rostral to the A1 area in the ventrolateral reticular formation. These cells, which correspond in position to PNMT-containing cells in the rat, appear to project to both thoracic and lumbar segments of the spinal cord. In contrast, spinally projecting neurons within the nucleus tractus solitarius originated from different subnuclei according to their segmental destination. New information about the organization of medial reticulospinal and vestibulospinal pathways was also obtained.     

Phase II evaluation of dianhydrogalactitol in the treatment of advanced non-squamous cervical carcinoma

Summary In an on-going Phase II evaluation, dianhydrogalactitol (NSC 132313) was administered intravenously to 28 patients with advanced or recurrent non-squamous cell carcinoma of the cervix. The initial dosage was 60 mg/m²/wk with escalation to 75 mg/m²/wk if there were no adverse effects. Twenty-seven patients were evaluable for toxicity and response. There was one complete response and one partial response. Adverse effects were not infrequent but tolerable.     

Phase II trial of cisplatin as second-line chemotherapy in patients with advanced or recurrent endometrial carcinoma. A Gynecologic Oncology Group study

Twenty-five patients with advanced or recurrent endometrial carcinoma no longer amenable to control with surgery, radiotherapy, hormonal therapy, or higher-priority chemotherapy were treated with cisplatin 50 mg/m2 intravenously every 3 weeks. Only one objective response, a partial response, was observed among the 25 patients (4%). Twenty patients (80%) exhibited stable disease for more than 1 month, while four patients (16%) progressed less than 1 month after initiating chemotherapy. Adverse effects included leukopenia (28%), thrombocytopenia (40%), nausea and vomiting (74%), and azotemia (37%). Only one patient experienced life-threatening toxicity. Cisplatin thus appears tolerable but only minimally active when given at the dose and schedule tested to patients with endometrial carcinoma who have previously demonstrated progression of disease on chemotherapy with known activity.     

Deep venous thrombosis of the lower limb: experiences of thrombectomy within and outside the iliacofemoral segment]

A series of 23 venous thrombectomies of the lower limb is presented. In 19 instances indirect thrombectomy of the iliacofemoral segment was performed. 1 direct thrombectomy of the v. cava inferior led to full lumen restoration. Direct thrombectomy of the popliteal vein was attempted in 3 cases, resulting in phlebographic and clinical normalization in 2 instances. In no instance did pulmonary embolism occur during or after venous thrombectomy.     

Freeze-fracture analysis of plasma membranes of isolated astrocytes from rat brain

Plasma membranes of mature rat astrocytes separated by differential centrifugation have been reported to be intact, based on electron microscopic examination of thin plastic sections. However, the effects of the separation procedure on the internal structure of the plasma membranes are unknown. The degree of membrane integrity is of concern to us since our goal is the separation of astrocytic plasma membranes and characterization of the specific intramembranous particle groups called assemblies. We have taken advantage of the astrocyte membrane-marker, the assembly, in order to monitor, by freeze-fracture, the identity of the separated astrocytes and the integrity of their cell membrane. Since some processes of an astrocyte contain assemblies whereas other processes of the same cell do not, it was also necessary to determine if processes with assemblies were separated by this technique. Astrocytic cell membranes were also examined to determine if trypsinization or the mechanical disruption steps of the separation affected the intramembranous particles. Freeze-fracture of the plasma membranes revealed that the particles were rearranged resulting in patches of clumped intramembranous particles and areas of bare membrane. The assemblies were rearranged rather than lost from the membrane since they could be identified among the clumped particles. More astrocytic plasma membranes contained non-clumped, normally distributed particles in the trypsin treated fractions. The non-trypsinized fractions had more damaged astrocytes with aggregated intramembranous particles and much more cellular debris. We interpret the findings for the non-trypsinized astrocytes as due to greater mechanical stress placed on the cells during tissue disruption. Trypsin treatment lessens this stress, thereby, tending to preserve the normal distribution of intramembranous particles.     

Investigation and management of pulmonary infiltrates following bone marrow transplantation: an eight year review.

BACKGROUND--Although pulmonary infiltrates are common in bone marrow transplant recipients and add significantly to the morbidity and mortality of this group of patients, there is uncertainty as to the most appropriate investigation and a lack of information on the effects of investigations on management and outcome. METHODS--All bone marrow transplant recipients from one institution referred for respiratory investigation between 1982 and 1990 were reviewed. RESULTS--Of 204 bone marrow transplant recipients 27 developed pulmonary infiltrates which failed to respond to broad spectrum antibiotics. All were examined by bronchoscopy and bronchoalveolar lavage. A specific diagnosis was made in 20 cases, 17 with an infective cause and three with a non-infective aetiology. In 17 of the 27 episodes these investigations led to a positive change in treatment, but in only five did these changes result in patient survival beyond one month. Eighteen of the 20 deaths were due to progressive respiratory failure of an infective aetiology in 14 and non-infective in four. CONCLUSIONS--Bronchoscopy and bronchoalveolar lavage are effective in establishing a diagnosis, but the impact on overall survival is disappointingly poor.