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Biomedical subjects

W Chapman

Publications and source records attributed to W Chapman.

At least 37 records · Page 2Linked to original sources

Tumor proliferation and apoptosis in human uterine cervix carcinoma I: correlations between variables.

PURPOSE: Parameters for tumor proliferation and apoptosis were studied prospectively in 84 previously untreated patients with a diagnosis of carcinoma of the uterine cervix. MATERIALS AND METHODS: Tumor proliferation was assessed by in vivo labeling with bromodeoxyuridine (BrdU), followed by a biopsy of the tumor 4-10 h thereafter during an examination under anesthesia. The potential doubling time (Tpot) was obtained by deriving the BrdU labeling index (LI) and S-phase duration (Ts) using flow cytometry. The LI for BrdU and its staining pattern were also determined immunohistochemically. Apoptosis was assessed histologically using morphological criteria. RESULTS: Seven patients were excluded and the FIGO stages of the remaining 77 patients were as follows: IB and IIA, 20 patients; IIB, 29 patients; IIIB and IV, 28 patients. The median tumor diameter was 6 cm. There were 61 squamous cell, 11 adeno- and five adenosquamous carcinomas. Of the 63 patients in whom the tumor grade could be determined, 37 were well or moderately well differentiated and the remaining 26 were poorly differentiated. The median mitotic index (MI) was 0.7%. There were 43 diploid and 34 aneuploid tumors. Median values for Ts and S-phase fraction (SPF) were 9.9 h and 16%, respectively. The median BrdU LI by flow cytometry (LI-fc) was 6.7%. There was a significant correlation between LI-fc and LI by histology, although values for the latter (median 11.1%) were consistently higher than those determined by flow cytometry by a factor of 1.5. The median Tpot value was 5.0 days. The median apoptotic index (AI) was 1.0% and AI correlated positively with LI-fc. Median values for LI-fc increased with increasing tumor size and were 5.1%, 6.4%, 7.5% and 11.0% for tumors measuring < or = 4 cm, 4-6 cm, 6-8 cm and > 8 cm, respectively. The remaining proliferation parameters, however, showed no correlation with tumor size, stage, grade or histologic type. CONCLUSIONS: In carcinomas of the cervix, tumor proliferation is positively associated with apoptosis and tumor size. These findings suggest that parameters for tumor proliferation and apoptosis are associated with tumor progression and may thus be predictive of clinical outcome.

Adenocarcinoma↗

Bilateral lymphangiomas of the ovary: an immunohistochemical characterization and review of the literature.

Lymphangiomas of the ovary are rare tumors, with only 13 cases reported. The diagnoses of these tumors have been based on histologic findings without immunohistochemical confirmation of endothelial cell origin. It is uncertain if these tumors are true neoplasms or if some represent reactive lesions. In this report, the literature is reviewed, and a 53-year-old woman with bilateral ovarian lymphangiomas is described. The ovarian masses were composed of numerous, thin-walled, cystic spaces containing a proteinaceous fluid, mature lymphocytes, and occasional erythrocytes. The cyst walls were lined by flat, benign-appearing cells that were immunoreactive for factor VIII-related antigen, CD34, and CD31. Further examination of the specimen showed absent fallopian tube fimbriae, tuboovarian adhesions, and chronic follicular salpingitis, suggesting that the lymphatic proliferation in the ovaries was a reactive change secondary to impaired regional lymphatic drainage.

Antigens, CD34↗

Renal function in primary liver transplant recipients receiving neoral (cyclosporine) versus prograf (tacrolimus).

Immunosuppressive efficacy of Neoral and Prograf following primary hepatic transplantation was comparable. Incidence of rejection episodes, infectious complications, hypertension, and postoperative diabetes mellitus was comparable. Although clinical use of both immunosuppressants was associated with early compromise in renal function, no progressive renal dysfunction was observed.

Analysis of Variance↗

Impact of Sandimmune, Neoral, and Prograf on rejection incidence and renal function in primary liver transplant recipients.

Following primary liver transplantation, immunosuppressive efficacy of Neoral and Prograf was similar and superior to that of Sandimmune. Rejection incidence was statistically increased with Sandimmune therapy. Incidence of hypertension, posttransplant diabetes mellitus, and infectious complications was not statistically different. Although early compromise in renal function was associated with Sandimmune, Neoral, and Prograf immunosuppression, no progressive renal dysfunction was identified.

Adult↗

Oxygenation predicts radiation response and survival in patients with cervix cancer.

BACKGROUND AND PURPOSE: Hypoxia appears to be an important factor in predicting tumor relapse following radiation therapy. This study measured oxygenation prior to treatment in patients with cervix cancer using a polarographic oxygen electrode to determine if oxygenation was an important prognostic factor with regard to tumor control and survival. MATERIALS AND METHODS: Between May 1994 and June 1997, 74 eligible patients with cervix cancer were entered into an ongoing prospective study of tumor oxygenation prior to primary radiation therapy. All patients were evaluated with an Eppendorf oxygen electrode during examination under anesthesia. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of pO2 readings of <5 mm Hg (abbreviated as HP5). RESULTS: The HP5 ranged from 2 to 99% with a median of 52%. With a median follow-up of 1.2 years, the disease-free survival (DFS) rate was 69% for patients with HP5 of < or =50% compared with 34% for those with HP5 of >50% (log-rank P = 0.02). Tumor size above and below the median of 5 cm was also significantly related to DFS (P = 0.0003) and patients with bulky hypoxic tumors had a significantly lower DFS (12% at 2 years) than either bulky oxygenated or non-bulky oxygenated or hypoxic tumors (65%, P = 0.0001). CONCLUSIONS: Hypoxia and tumor size are significant adverse prognostic factors in a univariate analysis of disease-free survival in patients with cervix cancer. A high risk group of patients with bulky hypoxic tumors have a significantly higher probability of relapse and death.

Adenocarcinoma↗

Effects on DNA integrity and apoptosis induction by a novel antitumor sesquiterpene drug, 6-hydroxymethylacylfulvene (HMAF, MGI 114).

6-Hydroxymethylacylfulvene (HMAF, MGI 114) is a new alkylating antitumor sesquiterpenoid with promising and often curative antitumor activity in vivo. This study examined the ability of the drug to damage cellular DNA, induce apoptosis, and affect the cell cycle of CEM human leukemia cells. No bifunctional lesions, interstrand DNA cross-links or DNA-protein cross-links were seen (by alkaline sedimentation and K+/SDS precipitation, respectively) when using up to 50 microM HMAF. The drug possibly formed some monoadducts, as DNA from drug-treated cells impeded primer extension by Taq polymerase, although only partial inhibition was seen even at 200 microM HMAF. HMAF also induced secondary lesions in cellular DNA, single-strand breaks that were detectable (by nucleoid sedimentation and alkaline sucrose gradient analysis) after a 4-hr treatment at HMAF levels as low as 2 microM, comparable to the growth inhibition IC50 value (1.7 microM). A post-treatment incubation of cells in drug-free medium generated substantial amounts of DNA double-stranded fragments of several kbp, suggesting apoptotic fragmentation (>30% of total DNA following treatment with 20 microM HMAF and a 17-hr post-treatment incubation). Chromatin condensation (by ultrastructural analysis) and induction of sub-G1 particles and apoptotic strand breakage (by multiparametric flow cytometry) confirmed induction of apoptosis by HMAF. HMAF preferentially inhibited DNA synthesis (IC50 approximately 2 microM), which is consistent with an S phase block, observed by cell cycle analysis. The pattern of apoptotic DNA fragmentation, inhibition of DNA synthesis, and blockage in the S phase suggests that these events play a role in the antiproliferative activity of HMAF.

Antineoplastic Agents↗

Use of the somatostatin analogue octreotide acetate in the treatment of encephalopathy associated with carcinoid tumor. Case report.

Carcinoid tumors may present in a variety of ways dependent on sites of disease and ectopic hormone secretion. This case report describes a patient having metastatic carcinoid tumor who developed encephalopathy of uncertain etiology. Treatment with the somatostatin analogue octreotide acetate resulted in dramatic improvement in his mental status. Several plausible mechanisms are discussed.

Adult↗

Randomized clinical trial of an absorbable stent for vasectomy reversal.

PURPOSE: More successful methods of vasectomy reversal would benefit those undergoing this treatment and might also increase the popularity of vasectomy. We conducted a randomized, prospective clinical trial of vasectomy reversal methods, comparing a new absorbable stent with 2-layer reattachment. MATERIALS AND METHODS: We studied 116 men seeking vasectomy reversal between November 1990 and March 1994. Data were analyzed primarily by intention to treat. RESULTS: Patients in the stent (64 cases) and no stent (52) randomized groups were similar in age distribution, age of spouses, years since vasectomy, proportion who had undergone prior vasectomy reversal and proportion who had previously achieved pregnancy. Operation time was more than 19 minutes shorter in the stent randomized group (p = 0.006). Fewer patients in the stent than the no stent group had patent vasovasostomies (81.0 versus 89.6%, respectively, p = 0.2) postoperatively. Fewer stent randomized patients had motile sperm (76.2 versus 81.3%, respectively, p = 0.5) and normal total motile sperm counts (49.2 versus 52.1%, respectively, p = 0.8) than did those without a stent. Conception occurred in 22 and 51% of all couples in the stent and no stent groups. The relative risk of conception among those in the stent group was 0.42 (95% confidence interval 0.24 to 0.71, p = 0.002). A Mantel-Cox log-rank test comparing pregnancies in each group according to the number of postoperative months revealed that the no stent group achieved more earlier pregnancies (p = 0.003). CONCLUSIONS: The 2-layer microscopic vasovasostomy results in greater pregnancy rates than vasovasostomy using the absorbable stent.

Absorption↗

The unidentified interstellar infrared bands: PAHs as carriers?

Infrared emission spectra of gas-phase naphthalene and pyrene have been measured in the range of 3 to 7.5 micrometers with ultraviolet laser desorption-excitation and a spectroscopic technique featuring single-photon counting in the infrared. The spectra were compared with the unidentified infrared emission bands that are observed in many astronomical objects. Marked discrepancies between those observations and the laboratory emission spectra in the wavelengths and relative intensities of principal spectral features led to the conclusion that small neutral unsubstituted polycyclic aromatic hydrocarbons cannot be the carriers of the unidentified infrared emission bands.

Astronomy↗

In vivo depigmentation by hydroxybenzene derivatives.

Certain mono- and dihydroxybenzene derivatives are selectively cytotoxic for melanocytes in vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxicity/hair depigmentation in C57Bl mice by injection of 0.032-1.0% p-t-butylcatechol (tBC) or p-hydroxyanisole (MMEH) in physiological saline. No depigmentation occurred on injection of 3,4-dihydroxyphenylalanine (DOPA) or 3,4-dihydroxyphenylacetic acid (DOPAC). Light- and electron-microscopic examination of biopsy specimens taken from depigmented areas indicates selective melanocyte damage as early as 2 h post-injection. Melanocytes from anagen hair are most susceptible to depigmentation. All four compounds are substrates for tyrosinase, but only tBC and MMEH generate their respective isolable 1,2-benzoquinones, tBCQ and MMEHQ. These caused depigmentation in C57Bl mice to a comparable degree to the parent compounds. DOPA- and DOPAC-quinones (DOPAQ and DOPACQ) are not spectroscopically detectable in solution, suggesting extremely low steady-state levels of these compounds. The net observed rate of reaction of the respective 1,2-quinone with 300 microM bovine serum albumin (BSA) in vitro varies widely, with tBCQ >> MMEHQ = DOPACQ >> DOPAQ. The results are consistent with a mechanism involving attack of -SH on melanosomal proteins and/or enzymes by tyrosinase-generated 1,2-quinones. This mechanism evidently differs from that involved in in vitro hydroxybenzene melanocytotoxicity of melanoma cells, in which active oxygen intermediates generated by hydroxybenzene autoxidation play a significant role. The most reliable prognosticator of in vivo depigmentation appears to be the ability of the depigmenter to form a spectroscopically stable 1,2-quinone which is capable of reacting with protein -SH.

3,4-Dihydroxyphenylacetic Acid↗

Repair of a traumatically amputated penis with return of erectile function.

Repair of the amputated penis may be successful using macroscopic and microscopic surgical realignments. However, to date, no one has reported return of erectile function documented by nocturnal penile tumescence. We report a case of traumatically amputated penis with microscopic repair and return of erectile function documented by nocturnal penile tumescence. In addition, the current literature regarding microscopic versus nonmicroscopic repair is reviewed.

Adult↗

Four cases of traumatic optic nerve blindness in the horse.

Traumatic optic nerve atrophy is characterised clinically by a unilateral or bilateral sudden onset of blindness. Dilated, fixed pupils and a lack of a menace reflex are the only abnormalities noted soon after the trauma. Within three to four weeks the optic disc becomes paler and the retinal vasculature is markedly decreased. The pathological lesion is a rupture of the nerve axons from stretching forces produced by the posterior movement of the brain against the fixed canalicular portion of the optic nerves. Medical therapy has not been successful.

Animals↗

Cutaneous metastatic adenocarcinoma of gallbladder origin.

Cutaneous metastases developed in a 74-year-old woman from an adenocarcinoma of the gallbladder. A biopsy specimen of a cutaneous nodule showed the presence of systemic cancer. Results of a histopathologic examination, along with the autopsy findings, established that the cutaneous metastasis was of gallbladder origin. This article reports the extreme rarity of metastases from a cancer of the gallbladder to the skin.

Adenocarcinoma↗

Splenic infarction and spontaneous rupture of the spleen after therapeutic embolization.

Patients with major hematologic disorders who have hypersplenism and alterations in their immune mechanism are subject to a higher incidence of bacteremia after embolization procedures. In certain instances, these infectious complications can be fatal. Medical splenectomy for hematologic disorders is sometimes complicated by massive splenic infarction and spontaneous rupture; spontaneous rupture appears to be a function of both infarct size and underlying infectious complications. Prophylactic measures can be employed to avoid these complications after interventional splenic embolization.

Abscess↗