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Biomedical subjects

P Nichols

Publications and source records attributed to P Nichols.

At least 19 recordsLinked to original sources

Portal vein thrombosis complicating endoscopic variceal sclerotherapy. Convincing further evidence.

Portal vein thrombosis occurred in a patient who bled from gastric varices that developed after obliteration of esophageal varices by endoscopic sclerotherapy. This complication was recognized only at surgery when thrombectomy and endovenectomy preceded the successful placement of an end-to-side portocaval shunt. At histopathology, the presence of an amorphous, eosinophilic material staining negatively for fibrin and similar to sclerosant injected at sclerotherapy was observed within the clot. This latter finding, previously unreported, provides convincing evidence for the causal relationship of portal vein thrombosis to endoscopic sclerotherapy.

Esophageal and Gastric Varices

Epidemiology of paramphistomosis in cattle.

The epidemiology of paramphistomosis in cattle was studied using tracer calves in a subtropical location in eastern Australia. Two species of paramphistomes were present; Calicophoron calicophorum and Paramphistomum ichikawai. The former species was the most abundant. Gyraulus scottianus and Helicorbis australiensis acted as intermediate hosts, respectively. Paramphistome burdens varied seasonally and were dependent upon the number of infected host snails. Peak fluke burdens and clinical paramphistomosis occurred in late summer in year 1 and early winter in year 2. The peak fluke burdens coincided with prolonged inundation of the grazing areas resulting in rapid multiplication and infection of host snails, and the period after the inundated areas dried out. The prevalence of infection in snails was high in both years, peaking at 98% in year 1 and 58% in year 2. The main host snail, G. scottianus, aestivated and retained infection for at least 24 weeks in soil, and in vegetable debris on the surface of the soil, resulting in rapid reappearance of host snails and infective metacercariae after the onset of seasonal rain. Metacercariae survived on herbage for up to 12 weeks, depending on the environmental conditions. Paramphistome burdens in calves could be predicted from the prevalence of infection in the host snail, the water levels and an index of surface water on the grazing site. Control of paramphistomosis during and after flooding may be achieved by removal of susceptible cattle from pasture or regular treatment during these periods. Strategic treatment during the dry season may reduce contamination of snail habitats and infectivity of the pasture in the following wet season.

Animals

The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial.

We assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and Mo transitional cell carcinoma of the bladder (with or without squamous or glandular differentiation) to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection. For most patients chemotherapy was planned as 4 courses at 28-day intervals of 100 mg./M.2 cisplatin, 60 mg./M.2 doxorubicin and 600 mg./M.2 cyclophosphamide. A significant delay was shown in the time to progression (p = 0.0010) with 70% of the patients assigned to chemotherapy free of disease at 3 years compared to 46% in the observation group. Median survival time for patients in the chemotherapy group was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In addition to treatment groups, important prognostic factors included age, gender and lymph node status. The number of involved lymph nodes was the single most important variable. We recommend adjuvant chemotherapy for patients with invasive transitional cell carcinoma after definitive surgical resection.

Antineoplastic Combined Chemotherapy Protocols

L-type calcium channels may regulate neurite initiation in cultured chick embryo brain neurons and N1E-115 neuroblastoma cells.

The intracellular free Ca2+ concentration, [Ca2+]i, plays an important role in regulating neurite growth in cultured neurons. Insofar as [Ca2+]i is partly a function of Ca2+ influx through voltage-sensitive calcium channels (VSCC), Ca2+ entry through VSCC should influence neurite growth. Vertebrate neurons may possess several types of VSCC. The most frequently described VSCC types are usually designated L, T and N. In most preparations, these VSCC types respond differently to certain pharmacological agents, including Cd2+, Ni2+, the dihydropyridines nifedipine and BAY K8644, and the aminoglycoside antibiotics. We used these agents to study the role of Ca2+ influx in regulating neurite initiation and length in cultures of chick embryo brain neurons and N1E-115 mouse neuroblastoma cells. In chick neurons, nifedipine and Cd2+ (less than 50 microM), which have been reported to inhibit L-type channels, reduced neurite initiation, but not mean neurite length. Ni2+ (less than 100 microM), reported to inhibit T-type channels, had no effect on either initiation or length. Low concentrations of most aminoglycosides (less than 300 microM), reported to inhibit N-type channels, had no effect on neurite initiation, but high concentrations of streptomycin (great than 300 microM), reported to inhibit both L- and N-type channels, reduced neurite initiation. BAY K8644, which enhances current flow through L-type channels, had no effect except at high concentration (50 microM), which inhibited initiation. N1E-115 neuroblastoma cells have been reported to contain L-type and T-type channels, but thus far no channel similar to the N-type has been described. In cultured N1E-115 cells, nifedipine (5 microM), Cd2+ (5 microM), and streptomycin (200 microM) reduced neurite initiation, while nickel (50 microM) and neomycin (100 microM) did not affect initiation. None of these agents altered neurite length. In N1E-115 cells, whole-cell voltage clamp recordings showed that nifedipine and Cd2+ inhibited L-type channels but not T-type channels, while Ni2+ inhibited T-type channels but not L-type channels. Streptomycin slightly inhibited L-type channels but enhanced current flow through T-type channels. Neomycin slightly inhibited both channel types. These data indicated that neurite initiation in these two cell types may be modulated by Ca2+ influx through L-type channels, but not T- or N-type channels. Neurite length was not significantly influenced by any of the agents tested, suggesting that Ca2+ influx through VSCC may not affect neurite elongation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

The role of radical cystectomy in the management of high grade superficial bladder cancer (PA, P1, PIS and P2)

Between January 1979 and 1987, 411 consecutive patients were considered candidates for bilateral pelvic iliac lymph node dissection and radical cystectomy for the management of bladder cancer. From this group 160 were identified as having pathological stage P2 or less disease, including 11 who also had positive nodes. The 5-year actuarial survival rate for the respective stages at 95% confidence limits was 100% for stage P0/A, 80% for stage P1, 78% for stage P1 with stage PIS, 85% for pure stage PIS, 76% for stage P2 and 87% for stage P2 with stage PIS. Additionally, we identified a group of patients with stage P2 transitional cell carcinoma who were at significant risk for development of metastatic disease. Of 46 patients with stage P2 transitional cell carcinoma 18 had vascular space invasion resulting in 6 of 18 cancer-related deaths (33%). Our study demonstrates that radical cystectomy has been highly effective in curing patients with high grade superficial disease, including those with superficially invasive disease associated with nodal metastases.

Carcinoma, Transitional Cell

Parathyroidectomy in chronic renal failure: a nine-year follow-up study.

Seventy-three patients with chronic renal failure who underwent parathyroidectomy between March 1978 and April 1987 were reviewed. Thirty-four patients had undergone sub-total parathyroidectomy, and 39 patients had undergone total parathyroidectomy with parathyroid autograft into the forearm. Eight patients showed persistent hyperparathyroidism requiring a second surgical procedure. In all other patients there was highly statistical improvement in parathyroid hormone, total calcium, ionized calcium, alkaline phosphatase and a significant reduction in calcium x phosphate product. Histological evidence of osteitis fibrosa was present in 21 of 22 patients before surgery. Postoperatively, four showed complete resolution and improvement. Three patients developed histological evidence of osteomalacia during the study period. Only four of the 39 patients who underwent total parathyroidectomy with autograft had true recurrent hyperparathyroidism and only two of the 34 patients who underwent sub-total parathyroidectomy had recurrent disease, indicating that there is little to choose between the two techniques in the control of secondary hyperparathyroidism and its subsequent recurrence. In one patient with recurrence of hyperparathyroidism from a forearm parathyroid graft the histological picture was different from that of normal hyperplastic parathyroid tissue. Although it is probable that abnormal parathyroid tissue had been implanted there was no evidence of invasive growth into the forearm muscle. The most striking feature of long term follow-up was the difference in calcium x phosphate product in patients in whom vascular calcification increased compared to those patients with no change or regression of calcification. Mean calcium phosphate product in those patients with progressive vascular calcification was 4.93 for small and medium size vessels and 5.38 for large vessels compared to 4.10 for small and medium vessels and 4.09 for large vessels. In the former case the serum phosphate was 2.00 and 2.17 as compared to 1.75 or 1.73, suggesting that the aim in patients with end stage renal failure maintained by dialysis should be to control the serum phosphate concentration to 1.8 mmol or less and the calcium x phosphate product to less than 4.2.

Adult

Phase I study of combination recombinant interleukin-2 and interferon gamma in patients with advanced malignancies.

A phase I trial of interleukin-2 and interferon gamma combination treatment in patients with advanced malignancies was performed based on preclinical in vitro and in vivo data which demonstrated synergistic antitumor effect. The toxicities, immune parameters, and tumor responses are described. The clinical and biologic maximal tolerated doses were extrapolated from these data.

Adolescent

Detection of occult CNS involvement of follicular small cleaved lymphoma by the polymerase chain reaction.

A patient with follicular small cleaved lymphoma presented with an unusual clinical relapse in the central nervous system (CNS) without morphologic evidence of lymphoma cells in the cerebral spinal fluid (CSF). Molecular genetic analysis of the small number of cells in the CSF after in vitro DNA amplification by the polymerase chain reaction demonstrated the presence of an abnormal translocation sequence between chromosomes 14 and 18. A similar translocation could be detected from the original fixed archival lymph node biopsy and from a small proportion of circulating mononuclear cells. These results indicated that occult lymphoma cells were present in the CSF and peripheral blood. Secondary CNS lymphoma involvement was identified at autopsy. This case demonstrates the enhanced sensitivity of lymphoma diagnosis from poorly cellular specimens after in vitro DNA amplification.

Aged

Molecular analysis of Hodgkin's disease with abundant Reed-Sternberg cells.

The pathogenesis of Hodgkin's disease (HD) has been elusive largely because of the paucity of the Reed-Sternberg cells in comparison to large numbers of normal inflammatory cells in biopsy specimens. This report attempts to characterize Hodgkin's disease by studying subtypes with a high proportion of Reed-Sternberg cells and their variants. We found in 4 out of 6 cases, clonal heavy and light chain immunoglobulin (Ig) gene rearrangements. The Ig rearrangement results are compared with the proportion of RS cells seen in the biopsy specimens and the data are correlated with the current literature.

Cell Count

Stereotaxic biopsy diagnosis of central nervous system lymphoma.

Twelve cases of central nervous system lymphoma diagnosed by stereotaxic brain biopsy are reviewed to determine the most effective method to establish the diagnosis given the small amount of tissue obtained by this technique. The stereotaxic biopsy material was examined cytologically, histologically, and immunocytochemically. The diagnosis was established by a smear made at the time of biopsy in eight cases. Histologic sections were diagnostic of lymphoma in 11 of 12 cases. Accurate classification according to the Working Formulation was possible in six cases, with diagnosis of diffuse small non-cleaved non-Burkitt's in three, large cell immunoblastic in two, and mixed small and large cell type in one. Five additional cases were diagnosed as high-grade lymphoma but could not be further subclassified because of the small biopsy size or formalin fixation. Immunocytochemical stains for lymphoid markers on paraffin-embedded material confirmed the diagnosis in ten cases, and, in one of these, the demonstration of monoclonality on air-dried cytospins identified an atypical polymorphous lymphocytic population as neoplastic.

Adult

Elevated maternal serum alpha-fetoprotein in triploidy.

We report two cases of greatly elevated maternal serum alpha-fetoprotein (MSAFP) in pregnancies associated with a triploid fetus. The concentration of AFP in amniotic fluid and fetal serum was within the normal range. Determination of fetal karyotype provides the only definitive method of diagnosis. Prompt recognition is warranted in view of the high rate of severe preeclampsia in triploid pregnancy.

Adult

Complex chromosome rearrangements and congenital anomalies.

Congenital complex chromosome rearrangements (CCR) compatible with life are rare in man. Thus patients with CCR usually present considerable diagnostic difficulties both clinically and cytogenetically. We studied a 12-year-old mentally retarded male with minor congenital anomalies as described below and his first-degree relatives. The propositus had an unbalanced karyotype with eight break points and seven derivative chromosomes; two deletions, del(6) (q25----qter) and del(14) (q31----qter), and four translocations, t(2;11), t(5;15), t(6;11), t(6;20) were present. Parental chromosomes were normal; however, the mother had a few metaphases with abnormal chromosomes suggestive of chromosome instability. These findings and a review of reported patients with CCR are presented with regard to speculations about etiology, pathogenesis, phenotypic expression, and prognosis. Physicians should be aware of CCR and broader indications for cytogenetic studies appear warranted in view of these data.

Abnormalities, Multiple

Immunohistology of persistent generalized lymphadenopathy. Evidence for progressive lymph node abnormalities in some patients.

Immunohistologic analysis of cellular changes in serial lymph node biopsies of eight patients with persistent generalized lymphadenopathy (PGL) syndrome was performed and correlated with clinical and laboratory findings to better determine the natural history of human immunodeficiency virus (HIV) infection. The authors observed decreased follicle size and area in the second biopsies of six of the eight patients, associated in some with increased numbers of B-cells in medullary regions (four of eight) and more involuted follicles (four of eight). Five cases showed progressively increased paracortical areas in the second biopsies, with increased numbers of T-cytotoxic/suppressor cells and decreased T-helper cells. Seven of the patients also had a progressive loss of T-helper cells in the peripheral blood. These findings provide tissue and peripheral blood evidence for progressive immunologic deterioration in some patients with PGL.

AIDS-Related Complex