Anti-endotoxin therapy in primate bacteremia with HA-1A and BPI.

OBJECTIVE: The in vivo neutralizing activities of an anti-lipopolysaccharide (LPS) antibody HA-1A (Centoxin [Centocor, Malvern, PA]), a human immunoglobulin M monoclonal antibody, and of bactericidal/permeability-increasing protein (BPI), an endogenously produced human LPS-neutralizing protein, were studied in a primate model of lethal Escherichia coli bacteremia. SUMMARY BACKGROUND DATA: HA-1A has been used with variable success against LPS activity in some animal models and in a recently reported clinical trial. However, no data assessing the efficacy of this agent in subhuman primates is available. Bactericidal/permeability-increasing protein is a product of polymorphomononuclear cells (PMNs) that is stored in azurophilic granules and exhibits LPS-neutralizing activity in vitro and in some in vivo models. METHODS: Immediately after E. coli infusion and in a blinded fashion, three baboons were treated with BPI (5 mg/kg bolus infusion and 95 micrograms/kg/min infusion over 4 hr). Three animals received 3 mg/kg BW of HA-1A, whereas another three baboons received a placebo treatment. RESULTS: The BPI-treated animals demonstrated significantly (p < 0.03) lower circulating LPS-limulus amoebocyte lysate (LAL) activity compared with the control animals, but this reduction in LPS-LAL activity was not associated with improved survival. HA-1A treatment did not reduce LPS-LAL activity. However, both BPI and HA-1A treatment did attenuate the pro-inflammatory cytokine response. CONCLUSION: The current data suggests that incomplete neutralization of endotoxin activity does not alter mortality from severe bacteremia. Given the diversity of mediator production under such circumstances, a strategy of combination therapy in the form of anti-lipopolysaccharide and anticytokine treatment may be necessary to achieve optimal survival.     

Chemotherapy in recurrent and advanced cervical cancer.

Twenty-five patients, ranging from 21 to 61 years of age (median = 45 years), with histologically proven recurrent and advanced cervical cancer were treated with chemotherapy using a combination of bleomycin, ifosfamide, and cis-platinum (BIP). Twenty-one patients were evaluable for response. Ninety percent of patients achieved a subjective response. An objective response was noted in 14 of 21 (66.6%) patients: complete in 4 (19%) and partial in 10 (47.6%). Side effects were mainly nausea/vomiting, alopecia, myelosuppression, reversible encephalopathy, and impaired renal function. One patient died from the toxic effects of chemotherapy. These results indicate that BIP is an active combination in recurrent cervical cancer with acceptable toxicity.     

Surgical management of trismus due to Oral Submucous Fibrosis — Lysis of fibrotic bands with the KTP-532 Laser

Oral Submucous Fibrosis is an insidious, chronic disease affecting the oral cavity, sometimes the pharynx and rarely the tongue. 15 patients with Oral Submucous Fibrosis presenting with severe trismus were treated with lysis of the fibrotic bands with a KTP-532 Laser and adjunctive treatment with excellent results over a 12 month follow-up period.     

Retinoblastoma. A clinical, immunohistochemical, and electron microscopic case report

A 4-year, 9-month-old boy had a history of leukocoria of the right eye for approximately six months prior to admission. The other eye was normal. There was no family history of retinoblastoma. Funduscopy disclosed a large white mass extending from the nasal pars plana to the mid-pupillary zone and the posterior pole with a near total retinal detachment in the superior temporal quadrant. A B-scan ultrasound showed an echo dense area of the anterior portion of the mass. A CT scan showed intraocular tissue densities with no evidence of optic nerve involvement or extraocular extension. Immunohistochemistry of a fresh frozen portion of tumor revealed reactivity with antibodies directed against interphotoreceptor retinoid-binding-protein (IRBP), neuron-specific enolase, glial fibrillary acidic protein, S-antigen, focal reactivity with opsin, and scattered cytoplasmic staining for cyclic GMP and cyclic GMP phosphodiesterase. Biochemical analysis of fresh frozen tissue samples confirmed the presence of IRBP. Transmission electron microscopy disclosed occasional Flexner-Wintersteiner rosettes connected by zonula adherens-like junctions. These showed inner segment-like structures containing prominent mitochondria, portions of cilia and fragments of outer segment material. These data, along with the immunocytochemistry indicates a predominant neuronal nature of the tumor cells with significant photoreceptor-like differentiation.     

Bilateral posterior lens dislocation in Marfan's syndrome

Complete dislocation of the lens is a rare feature of Marfan's Syndrome. We observed four cases of bilateral complete posterior dislocation of the lens in established cases of Marfan's Syndrome over a one year period. An ophthalmologist may encounter infrequently, unilateral posterior dislocation in one eye and ectopia lentis in the other, but bilateral spontaneous posterior dislocation is rare. All our cases had associated vitreous degeneration with vitreous herniating into the anterior chamber. The pathogenesis of complete posterior dislocation in Marfan's Syndrome is discussed.     

A cell line from Wilms' tumour with deletion in short arm of chromosome II

A cell line (T3/73) from a Wilms' tumour has been established from a 9 month-old boy with aniridia. The tumour was removed in 1973. On histological examination a diagnosis of Wilms' tumour was made which showed undifferentiated areas, marked tubule formation and abundant striped muscle fibres. The tumour cells, which are fusiform, grew rapidly in culture without the addition of growth factors, and have undergone over 100 passages. Approximately 95% and 5% were positive for desmin and cytokeratin, respectively. The cell doubling time was 28 hr. Cytogenetic studies revealed a karyotype of 46,XY,del(11) (p12::p14). Although the cells stained very intensely with a monoclonal antibody that detects oncogene ras p 21 antigen, Southern blot analysis using c-Ha-ras as a probe failed to reveal an obvious deletion or amplification of either Ha-ras allele.     

Variability in cardiovascular and plasma norepinephrine responses to head-up tilt in healthy human subjects.

Eight healthy, young adult males underwent three separate, 10-min 70 degrees head-up tilts (HUT) over a period of nine days, in order to assess the intra- and inter-individual variability of cardiovascular and plasma norepinephrine (NE) responses to the manoeuvre. Cardiovascular parameters and plasma NE were measured in the basal state and at 2-min intervals during the HUT. The results indicate that: (1) the intra-individual variability is a smaller component of the total variability of both cardiovascular and plasma NE responses to HUT; (2) the variability in cardiovascular parameters is smaller than that in plasma NE levels, both basal and in response to postural stress; (3) there does not appear to be any difference in variability when expressed either as the maximal or the mean response to HUT; and (4) there does not appear to be an increase in the variability of the measured parameters over the duration of the HUT.