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Biomedical subjects

M Press

Publications and source records attributed to M Press.

At least 19 recordsLinked to original sources
PubMed1999

Elevated serum creatine kinase activity in a patient with acute pancreatitis.

A 62-year-old man presented with a five-day history of a 'flu-like' illness, epigastric pain and a state of increasing confusion. His serum values for amylase and glucose were grossly elevated, as was the creatine kinase (CK) activity, being 23 times above the upper limit of normal. CK-MB was less than 5% of his total CK activity. There was no past history of diabetes or recent history of intramuscular injections or injury. A diagnosis of acute pancreatitis complicated by hyperosmolar non-ketotic (HONK) diabetic pre-coma was made. The patient was treated with intravenous fluids, insulin and subcutaneous heparin. Normal values for serum amylase and CK activity were recorded with convalescence. This case indicates a possible association of a rise in total CK activity with acute pancreatitis complicated by HONK diabetic pre-coma. This observation was made in the absence of clinically evident muscle pathology.

Acute Disease↗
PubMed1997

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy.

PURPOSE/OBJECTIVE: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. METHODS AND MATERIALS: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. RESULTS: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response to this regimen (p = 0.010). CONCLUSION: The combination of c.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size, the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of c.i. 5-FU and radiotherapy in locally advanced breast cancer.

Adult↗
PubMed1997

Relevance of human papillomavirus screening in management of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the utility of human papillomavirus detection in identifying women with abnormal Papanicolaou smears who can be safely followed up with cytologic study only, we conducted a study to determine the sensitivity, specificity, and negative and positive predictive values of a Food and Drug Administration-approved human papillomavirus test kit for detection of cervical intraepithelial neoplasia in colposcopically directed biopsy specimens. STUDY DESIGN: We enrolled women with abnormal Papanicolaou smears referred to a colposcopy clinic serving indigent patients. All 1128 women had a referral Papanicolaou smear, a clinic Papanicolaou smear, and a sample for human papillomavirus deoxyribonucleic acid test; 1075 underwent colposcopically directed biopsies and endocervical curettage. We used the HPV Profile kit for human papillomavirus testing. RESULTS: Of 486 women with low-grade squamous intraepithelial lesions on Papanicolaou smear, 35.4% had high-risk human papillomavirus deoxyribonucleic acid detected, and of 592 with high-grade lesions, 44.4% had high-risk human papillomavirus detected. Among 527 women with biopsy specimens showing cervical intraepithelial neoplasia and in 267 with cervical intraepithelial neoplasia grades 2 or 3, 38.7% and 56.2% had high-risk human papillomavirus deoxyribonucleic acid detected. However, the sensitivity of human papillomavirus deoxyribonucleic acid detection to identify biopsy-confirmed cervical intraepithelial neoplasia grades 2 or 3 was 55.7%, and the positive predictive value of the test was only 34.9%. CONCLUSION: Human papillomavirus appears to be causally associated with cervical cancer but human papillomavirus screening does not appear to be of value to identify women with abnormal Papanicolaou smears who can be safely followed up with cytologic study alone.

Adolescent↗
PubMed1997

Telomerase activity in normal and neoplastic breast.

Telomerase activity is detected in the majority of human tumors and provides a mechanism to escape from proliferative limitations due to telomere loss. Similar to other studies, telomerase activity was detected with a modified telomeric repeat amplification protocol in the majority (76%) of 49 human breast cancer specimens, including most (75%) ductal carcinoma in situ specimens. There were no correlations between telomerase activity and tumor stage or estrogen/progesterone receptor status. In four of seven invasive tumors, telomerase expression seemed to be heterogeneous because not all microdissected regions were telomerase positive. Low levels of telomerase activity were also detected in a minority (17%) of breast specimens from patients without evidence of cancer. These findings suggest that telomerase activation can occur early in breast cancer progression and may be periodically down-regulated during subsequent progression.

Biomarkers, Tumor↗
PubMed1995

Search for optimal parent for recombinant vaccinia virus vaccines. Study of three vaccinia virus vaccinal strains and several virus lines derived from them.

Three vaccinia virus strains (Praha, DD--a DRYVAX Wyeth vaccine-derived virus-and LIVP) were examined for growth in various cell cultures and for virulence and immunogenicity in mice. The viruses did not differ by their growth rates in monkey kidney cells (CV-1), human diploid cells (LEP), rat TK cells (RAT 2) or primary dog kidney cells. The immunogenicity of Praha and DD viruses was similar, the virus LIVP was somewhat more immunogenic. In terms of virulence in 3-day-old mice, the DD virus was the most attenuated. Single-plaque progenies were derived from the original smallpox vaccines VARIE Sevac (strain Praha) and DRYVAX Wyeth and tested for the above markers and DNA restriction patterns. The results obtained demonstrated biological and molecular heterogeneity of the original virus populations. Close linkage was observed between immunogenic activity and virulence in 3-day but not in 3-week mice. The results indicate that smallpox vaccine preparations may serve as an abundant source of virus mutants.

3T3 Cells↗
PubMed1995

Myopathy in acquired partial lipodystrophy.

We describe two women with acquired partial lipodystrophy, one with significant myopathic symptoms and signs. Muscle biopsy of deltoid and quadriceps was performed in each case. The light microscopy findings were of type 1 and type 2 fibre hypertrophy, with an increase in intracytoplasmic fat in both cases. Electron microscopy showed normal fibres, with accumulations of electron-lucent fat droplets between the myofibrils. The cause of the lipodystrophies is uncertain, but myopathy may be a feature, and muscle biopsy studies may help in further defining the syndrome.

Adipose Tissue↗
PubMed1995

Expression of the c-kit proto-oncogene and its ligand stem cell factor (SCF) in normal and malignant human testicular tissue.

Recent findings suggest an important role of the proto-oncogene c-kit, a surface membrane receptor of the tyrosine kinase family, and its ligand stem cell factor (SCF) in normal spermatogenesis and possibly in the pathogenesis of certain testicular germ cell tumors. To further investigate this potential role, the expression of c-kit and SCF was studied in normal and malignant human testicular tissue specimens at the mRNA and protein level by Northern blot analysis and immunohistochemistry, respectively. The detection of the c-kit receptor in normal human germ cells and its natural ligand SCF in Sertoli cells suggests the presence of a local trophic regulatory system that may be active in human spermatogenesis. Additionally, c-kit expression was detected in the seminoma but not in the nonseminoma subtype of human testicular germ cell tumors (GCT). Stem cell factor was not expressed at the mRNA level in tissue from either subtype of GCT as determined by Northern blot analysis; however, the protein was detected immunohistochemically in the cytoplasm of rare tumor cells.

Cell Adhesion Molecules↗
PubMed1995

Testosterone deficiency myopathy.

Testosterone is recognized to have a positive effect on nitrogen balance and muscle development in hypogonadal men, but significantly myopathy secondary to testosterone deficiency has been reported only rarely. We describe a patient who presented with a myopathy associated with testosterone deficiency, and who demonstrated a significant functional and myometric response to treatment.

Aged↗
PubMed1994

A carboxy-terminal portion of the preS1 domain of hepatitis B virus (HBV) occasioned retention in endoplasmic reticulum of HBV envelope proteins expressed by recombinant vaccinia viruses.

The large envelope glycoprotein (L protein) of Hepatitis B virus (HBV) contains the preS1 domain, which is responsible for retention of the protein in the endoplasmic reticulum. To identify sequences of the preS1 domain involved in this phenomenon we constructed vaccinia virus-HBV recombinants containing the gene for L protein in which the preS1 coding sequence had been partially deleted. The retention of L protein in the endoplasmic reticulum was found to be mediated by a sequence contained within a region of 35 amino acids of the preS1 C-terminus, and not exclusively by amino acid sequences of the N-terminus of the preS1 domain as proposed by Kuroki et al. (Mol. Cell. Biol. 9, 4459-4466, 1989). Our finding could be explained by a specifically VV promoter sequence leading to exclusive synthesis of L or deleted (delta)L proteins, respectively. The ability of the coexpressed HBV S protein to facilitate export of the delta L proteins was demonstrated by coinfection experiments.

Base Sequence↗
PubMed1993

Evaluating the effect of age on endometrial responsiveness to hormone replacement therapy: a histologic ultrasonographic, and tissue receptor analysis.

OBJECTIVE: Our objective was to characterize the endometria of women of various ages placed on similar estrogen/progesterone replacement regimens prior to attempted donor embryo transfer using histologic, ultrasonographic, and steroid receptor markers in order to determine if advancing age has a detrimental effect on uterine responsiveness to pharmacologic sex steroid replacement therapy. STUDY DESIGN: This was a prospective open clinical trial. Functionally agonadal women aged 25 to 60 years receiving hormone replacement therapy underwent transvaginal ultrasound examination of the uterus followed by a timed endometrial biopsy on artificial cycle day 21. Endometrial histology and estrogen and progesterone receptors were analyzed from biopsy material. Subjects were assigned to three groups according to age: Group I, aged 25 to 39 years (n = 48); Group II, aged 40 to 49 years (n = 61); and Group III, aged 50 to 60 years (n = 13). Endometrial preparation was accomplished in all patients using the same sequential regimen consisting of oral micronized estradiol and intramuscular progesterone. RESULTS: Similar histologic, ultrasonographic, and steroid receptor characteristics were noted in all groups of patients regardless of age. A normal appearing midluteal secretory endometrium was demonstrated histologically in 85% of biopsies. However, 15% of biopsies exhibited intraluminal papillary excrescences within the glands and/or increase in the normal gland-to-stroma ratio. Three patients, one from each group, did not initially respond to replacement therapy and required further treatment. CONCLUSION: Functionally agonadal women exhibit normal or near-normal endometrial responses to sex steroid replacement therapy designed to imitate the natural cycle through the sixth decade of life.

Adult↗
PubMed1993

The magnitude of the hypercholesterolemia of hypothyroidism is associated with variation in the low density lipoprotein receptor gene.

To assess whether the variable extent to which patients with hypothyroidism become hypercholesterolemic was associated with variation in the genes for the low density lipoprotein (LDL) receptor or apolipoprotein-B, we investigated prospectively 52 patients with primary hypothyroidism treated with L-T4. There was significant reduction in cholesterol, high density lipoprotein cholesterol, LDL cholesterol, and apolipoprotein-A1 and -B after thyroid hormone replacement. The reduction in cholesterol was associated significantly with the magnitude in the reduction of serum TSH levels (P < 0.001) and the variable AvaII restriction site in exon 13 of the LDL receptor gene. For a given reduction in TSH, patients of genotype -/- (no restriction site) demonstrated a reduction in serum LDL cholesterol that was 4-fold greater than that of patients homozygous for the AvaII restriction site (genotype +/+), with heterozygous (+/-) patients showing an intermediate response. The hypocholesterolemic response was significantly greater in patients of the -/- genotype than in patients carrying the +allele (genotypes +/- and +/+; for LDL cholesterol, P < 0.01; for cholesterol, P < 0.05). No such relationship was observed with a variation at any other polymorphic site studied (four in the LDL receptor gene and two in the apolipoprotein-B gene). The magnitude of the decrease in high density lipoprotein cholesterol and apolipoprotein-A1 and -B was independent of the AvaII genotype, the effect of which was specific to LDL cholesterol. Variation within the LDL receptor gene appears to influence the magnitude of both the hypercholesterolemia of hypothyroidism and, consequently, the reduction of serum LDL cholesterol in response to L-T4. Thus, it may be possible to predict which hypothyroid patients are at greatest risk for coronary artery disease.

Adult↗
PubMed1992

Effect of growth hormone treatment on hyperinsulinemia associated with Turner syndrome.

To determine whether the insulin resistance in patients with Turner syndrome, which may be exaggerated by treatment with human growth hormone, leads to excessive insulin secretion, we applied the hyperglycemic glucose-clamp technique to produce a standard hyperglycemic stimulus (6.9 mmol/L, or 125 mg/dl, greater than fasting plasma glucose level for 120 minutes) in seven patients with Turner syndrome and in seven healthy children. These studies were repeated in the patients after 6 to 12 months of therapy with growth hormone. Fasting plasma levels of insulin were comparable in control subjects and patients before therapy but increased significantly in the patients after 6 to 12 months of treatment with growth hormone. Despite identical glucose increments in the two groups during the glucose-clamp procedure, both first- and second-phase insulin responses were significantly greater in the patients than in the control subjects. Moreover, the hyperinsulinemic responses to glucose were markedly exaggerated in the patients after their treatment with growth hormone, reaching values (first phase 474 +/- 100 pmol and second phase 826 +/- 100 pmol; p less than 0.02 vs pretreatment values) that were almost threefold greater than those in control subjects (p less than 0.001). Nevertheless, the rate of insulin-stimulated glucose metabolism during the last 60 minutes of the clamp procedure was similar in all three groups of studies. Glycosylated hemoglobin, total cholesterol level, and blood pressure remained normal in patients after therapy with growth hormone. We conclude that glucose-stimulated insulin response is increased in patients with Turner syndrome and that these alterations are further exaggerated by treatment with growth hormone. These hyperinsulinemic responses appear to compensate for reductions in insulin sensitivity.

Adolescent↗