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Biomedical subjects

C L Gonzalez

Publications and source records attributed to C L Gonzalez.

29 records · Page 2Linked to original sources

Composite lymphoma. A clinicopathologic analysis of nine patients with Hodgkin's disease and B-cell non-Hodgkin's lymphoma.

Nine patients had composite lymphoma in which Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) involved the same anatomic site. Two of these patients had relapses of their tumors. In one, the initial biopsy specimen contained follicular and diffuse large cell NHL with unclassifiable HD, but the relapse showed diffuse large cell NHL with nodular sclerosis HD. In the other patient, both biopsy specimens showed follicular mixed NHL; the HD component in the initial biopsy specimen was nodular sclerosis, whereas, at relapse, it had the appearance of interfollicular HD. In the remaining seven patients, the HD component was subclassified as nodular sclerosis (three specimens) or mixed cellularity (three specimens), or it was unclassifiable (one specimen). The NHL component was categorized as diffuse large cell (two specimens), diffuse large cell immunoblastic (two specimens), follicular and diffuse large cell (one specimen), diffuse mixed small and large cell (one specimen), and lymphocytic lymphoma of intermediate differentiation (modified Rappaport classification) (one specimen). Paraffin section immunoperoxidase studies were done on the NHL component in eight patients (nine specimens) and on the HD component in six patients (seven specimens). In each of these, the NHL component was leukocyte common antigen (LCA) positive and Leu-M1 negative. In addition, the neoplastic cells were L26 positive and UCHL-1 negative, indicating a B-cell phenotype. In five of seven immunophenotyped cases, Reed-Sternberg (RS) and Hodgkin's (H) cells from the HD areas were Leu-M1 positive and LCA negative, reflecting an immunophenotype that is typical of non-lymphocyte-predominant HD. In two specimens, the malignant cells were negative for Leu-M1 and LCA (with positive internal controls). Composite lymphomas composed of HD and NHL are unusual, and cases of coexistent HD of the non-lymphocyte-predominant subtype and NHL are even less common. The results of the current study and a review of the literature indicate that this phenomenon usually involves a B-cell NHL that coexists with HD, perhaps further suggesting a close relationship between the malignant cells of HD (RS and H cells) and B lymphocytes.

Adult↗

T-cell lymphoma involving subcutaneous tissue. A clinicopathologic entity commonly associated with hemophagocytic syndrome.

Eight cases of T-cell lymphoma localized primarily to the subcutaneous adipose tissue are described, five of which were referred in consultation with a benign diagnosis having been made or suggested. All patients presented with 1-12-cm-diameter subcutaneous nodules, which preferentially involved the extremities in six individuals. Histologically, the lesions were reminiscent of panniculitis and were composed of a mixture of small and large atypical lymphoid cells (large cells predominated in four cases) infiltrating between adipocytes. Focally, sheets of tumor cells were found. Karyorrhexis, fat necrosis, and benign histiocytes were present in all cases. Involvement of small blood vessels was found in seven cases, but the infiltrates were not primarily angiocentric, and angiodestruction was minimal or absent. Immunophenotypic analysis (paraffin or frozen sections) in all cases showed that the atypical cells were of T-cell phenotype. Frozen-section studies demonstrated a mature T-cell phenotype with evidence of pan-T-cell antigen loss in two of five lesions. Genotypic analysis demonstrated a rearrangement of the T-cell receptor beta-chain gene in one (possibly two) biopsies of three cases studied. All patients had some evidence of hemophagocytosis during their clinical course. Six patients developed a florid hemophagocytic syndrome, fatal in five patients. Autopsies were done in all of the expired patients, and all had residual subcutaneous lymphoma and a hemophagocytic syndrome. Dissemination to nonsubcutaneous sites did not occur. Three patients are currently alive without evidence of lymphoma after aggressive chemotherapy (mean follow-up, 12 months). These results suggest that T-cell lymphomas that are primarily localized to the subcutaneous tissue may represent a distinct clinicopathologic entity. Initial biopsy findings may be misinterpreted as benign. A hemophagocytic syndrome commonly supervenes that may be secondary to lymphokine production by the malignant cells or related to the destruction of normal cells at subcutaneous sites.

Adult↗

The histiocytoses: clinical presentation and differential diagnosis.

The histiocytoses, whether reactive or neoplastic, can be related histologically and immunophenotypically to their normal counterparts within the histiocytic system. This system has two subsets: The dendritic (antigen-presenting) cells and the phagocytic histiocytic (antigen-processing) cells. Dermatopathic lymphadenitis and Langerhans cell histiocytosis (histiocytosis X) are reactive proliferative disorders of dendritic cells. Malignancies of dendritic cells exist, but they are very rare. Benign proliferations of phagocytic histiocytes include the hemophagocytic syndromes, both familial and reactive, as well as sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) and histiocytic necrotizing lymphadenitis (Kikuchi's disease). Neoplasms of phagocytic histiocytes include acute monocytic leukemia and the very rare entities, malignant histiocytosis and true histiocytic lymphoma. The latter must be distinguished from sinusoidal, large cell anaplastic lymphomas.

Diagnosis, Differential↗

Effect of antenatal exposure to paroxetine (paxil) on growth and physical maturation of mice offspring.

OBJECTIVE: Our purpose was to determine, in a placebo-controlled manner, whether antenatal exposure to paroxetine affected long-term growth and physical maturation of mice offspring. METHODS: Forty-one CD-1 mice consumed paroxetine (n = 21) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. The daily dose of paroxetine (Paxil; 30 mg/kg/d) was known to achieve concentrations in the serum equivalent to the upper therapeutic level in humans and in the fetal brain equivalent to that of the adult mouse. Growth and physical maturation of the offspring were compared by paired t-test, Welch's corrected test, and Fisher's exact test. RESULTS: The maternal weight gain, litter sizes, number of fetal resorptions, and gestational age at delivery were not different between the paroxetine and the placebo-exposed offspring. Newborn pups exposed to paroxetine were more likely to have low birthweights (1.65 gm vs. 1.70 gm; P < 0.05) and narrower heads (7.7 mm vs. 8.1 mm; P < 0.05). Body weight, body length, and head circumference measurements increased in a manner that was indistinguishable between the two groups of offspring, regardless of gender. No differences in achievement of physical milestones (lower incisor eruption, eye opening, and development of external genitalia) were noted between the two groups. The reproductive capability and the perinatal outcomes of the second-generation offspring were unaffected by paroxetine exposure. CONCLUSION: A clinically relevant dose of paroxetine, when given throughout gestation, did not affect long-term growth and physical maturation of mice offspring.

Aging↗

Chronic prenatal exposure to paroxetine (Paxil) and cognitive development of mice offspring.

This study investigated the impact on cognitive development in CD-1 mice from chronic prenatal exposure to the antidepressant paroxetine. CD-1 mice were given either paroxetine as 30 mg/kg/day or a placebo in food bars for 2 weeks before mating and throughout gestation. One offspring per gender from each litter was tested on each of the following tasks: tube runway, spatial maze, passive avoidance chamber, and water straight runway followed by an unforced decision maze. Learning occurred in both genders in all tasks (p<0.001) with no significant differences between treatment groups at the final learning session. Juvenile runway was the only task in which the paroxetine-exposed males demonstrated a learning rate that was slower than the placebo-exposed offspring (p=0.06). Post learning sessions did not show any significant treatment differences during the juvenile and adult periods during the water straight runway, mazes, and avoidance chamber tasks. In conclusion, chronic prenatal exposure in mice of paroxetine did not impact cognition on select tasks.

Animals↗

Impact of hypericum (St.-John's-wort) given prenatally on cognition of mice offspring.

This study investigated the cognitive impact of prenatal exposure to the herbal antidepressant hypericum in CD-1 mice. Hypericum (182 mg/kg/day) or a placebo was consumed in food bars for 2 weeks before mating and throughout gestation. The hypericin content in our hypericum formulation was in the middle range of standardized hypericum products. One offspring per gender from each litter (hypericum 13, placebo 12) was tested on each of the following tasks: juvenile runway with adult memory, adult Morris maze, adult passive avoidance, or adult straight water runway followed by a dry Cincinnati maze. Learning occurred in both genders in all tasks (P<.003) with no significant differences between treatments at the final trial. Female offspring exposed to hypericum, rather than to a placebo, required more time to learn the Morris maze task (P<.05). Postlearning sessions did not show any significant differences. In conclusion, prenatal exposure to a therapeutic dose of hypericum did not have a major impact on certain cognitive tasks in mice offspring.

Animals↗

Effect of in utero exposure to betamethasone on motivation/anxiety testing in mice offspring.

In utero exposure to a single dose of the long-acting corticosteroid betamethasone at GD 14 has been shown to induce specific differences in motivation/anxiety testing among offspring. Because multidosings are desired to enhance fetal lung maturation, our objective was to compare effects of multidosings of betamethasone with a placebo on postnatal tests of motivation and anxiety. Sixty gravid CD-1 mice were randomly assigned to receive one of six treatment regimens (n = 10) that consisted of a single or a double SC dosing of either betamethasone (Celestone soluspan 0.2 mg on GD 14; 0.1 mg on GD 13 to 16; 0.1 mg b.i.d. on GD 14 and 15; 0.1 mg b.i.d. on GD 13 to 16) or saline (0.25 ml on GD 13 to 16; 0.25 ml b.i.d. on GD 13 to 16). The percent of pups exhibiting separation vocalization was temporarily less at PND 5 after betamethasone exposure to four doses (p < 0.05) and to eight doses (p < 0.01). The percents of pups being successful in homing (PND 9) and in responding to startle stimulation (PND 12-15) were not different between the betamethasone-exposed and placebo-exposed groups. Exploratory performance in the radial arm maze revealed no delay in the activities of juvenile and adult offspring exposed to betamethasone. The percent of male offspring that fought as juveniles and as adults was not different between the betamethasone-exposed and the placebo-exposed groups. The previously reported altered responses using the elevated plus maze, among juvenile and adult offspring, after a single dose of betamethasone was not replicated in this multidose study. These data indicate that prenatal exposure to betamethasone did not affect the mouse offspring's long-term responses to motivation/anxiety testing.

Animals↗

A placebo-controlled, blinded comparison between betamethasone and dexamethasone to enhance lung maturation in the fetal mouse.

OBJECTIVE: To compare the effects of betamethasone and dexamethasone used to enhance lung maturity of the fetal mouse. METHODS: Adult CD-1 mice were administered a single dose of either a placebo or different strengths of betamethasone (0.01, 0.025, or 0.10 mg) or dexamethasone (0.025 or 0.10 mg) on day 14.0 (74%) of gestation. The eight gravid mice in each treatment cohort were killed on day 16.5 to assess fetal lung maturity (histologic changes and respiratory patterns) in a blinded manner. Another ten gravid mice in each treatment group were allowed to deliver spontaneously to assess perinatal outcomes. RESULTS: Compared with the effects from placebo exposure, the 0.10-mg doses of both betamethasone and dexamethasone demonstrated enhanced histologic maturational changes and improved neonatal respiratory efforts. Betamethasone was twofold to threefold more potent than dexamethasone. The fetal crown-rump lengths and the fetal body, lung, and heart weights were indistinguishable among the three treatment groups. Compared with the fetal liver weight in the placebo group (55.0 +/- 2.2 mg), the liver was less heavy after exposure to 0.10 mg of betamethasone (45.6 +/- 2.0 mg; P < .005), 0.025 mg of dexamethasone (47.6 +/- 1.7 mg; P < .02), or 0.10 mg of dexamethasone (43.8 +/- 1.5 mg; P < .001). No significant differences were observed between the 0.10-mg treatments of either corticosteroid and placebo for the duration of gestation, litter size, survival rate, birth weights, or weight gains to postnatal day 26. CONCLUSION: A single subcutaneous dose of 0.10 mg of betamethasone was twofold to threefold more potent than dexamethasone in accelerating fetal lung maturity without impairing fetal survival or weight gain. The unexpected finding of a reduced fetal liver weight with either corticosteroid warrants clinical correlation.

Animals↗

Detection of hepatitis B virus DNA by the polymerase chain reaction in anti-HBe positive chronic hepatitis B patients.

Detection of HBV-DNA by PCR was compared with other serological markers (HBsAG, HBeAg and anti-HBe) in a series of 49 Chronic Hepatitis B patients, including 12 with a spontaneous clearance of HBsAg. None of these HBsAg negative cases were PCR positive, but 33/37 (89.2%) HBsAg positive cases were PCR positive (p < 0.0001). Among HBsAg positive samples, nine cases were HBeAg positive and anti-HBe negative, all of them PCR positive. Other 3 patients were HBeAg and anti-HBe positive and these cases were also found PCR positive. A third group included 21 patients anti-HBe positive and HBeAg negative: 19 of them were PCR positive and 2 were PCR negative. The last 4 cases were HBeAg and anti-HBe negative, two of them were PCR positive. The detection of anti-HBe viremic cases in the present series suggest that preC variants could occur in our country. In conclusion, the integrated phase of chronic hepatitis B seems to be less frequent than it was assumed, when only HBeAg or dot blot hybridization techniques were used. The new term "low replication phase" might favorably replace the former "integrated phase".

Base Sequence↗