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Biomedical subjects

N Stone

Publications and source records attributed to N Stone.

At least 55 records · Page 3Linked to original sources
PubMed1997

Localized amyloidosis of the seminal vesicle. Possible association with hormonally treated prostatic adenocarcinoma.

OBJECTIVE: Localized seminal vesicle amyloidosis is an unusual finding in surgical pathology material. Previous studies have demonstrated that the amyloid is directly produced by the seminal vesicle epithelial cells. We investigated the possible association of seminal vesicle amyloid in patients hormonally treated for prostate carcinoma. METHODS: Cases were collected from over 200 prostate needle biopsies, seminal vesicle biopsies, and prostatectomy specimens from the surgical pathology files at The Mount Sinai Hospital, New York, NY. None of the patients with seminal vesicle amyloidosis had a chronic inflammatory disorder, serum or urine protein abnormalities, or other identifiable masses. RESULTS: Six cases of localized seminal vesicle amyloidosis were found in the surgical pathology material examined. Five of the six cases had prostatic carcinoma, and one case was seen in a biopsy for benign prostatic hyperplasia. Four of the five carcinoma cases had prior hormonal treatment (luteinizing hormone-releasing hormone agonist with an antiandrogen agent, and one patient, in addition, had received radiotherapy). The amyloid deposits were limited to the seminal vesicle lamina propria without involvement of vascular walls. The amyloid reacted with Congo red staining that was sensitive to potassium permanganate. Immunohistochemically, all cases were negative for AA amyloid, beta 2-microglobulin, and kappa and lambda light chains. CONCLUSION: We raise the possibility that in some instances, prior hormonal therapy may act as a seminal vesicle epithelial stimulant for the elaboration of this protein.

Adenocarcinoma↗
PubMed1996

Cisplatin-based chemotherapy in renal transplant recipients. A case report and a review of the literature.

BACKGROUND: Renal transplant recipients have a high incidence of cancer. The main side effect of cisplatin, nephrotoxicity, has special implications in renal transplant recipients. This is particularly true in view of the routine use of cyclosporine as an immunosuppresant. Nephrotoxicity is also one of the main side effects of cyclosporine. METHODS: We report a patient with a renal allograft who was receiving cyclosporine for immunosuppression and developed metastatic transitional cell carcinoma of the bladder and was treated with cisplatin-based chemotherapy. The literature regarding cisplatin-containing chemotherapy in patients with different cancers and a single transplanted kidney is reviewed. RESULTS: The patient received four cycles of methotrexate, vinblastine, doxorubicin, and cisplatin while on continuous cyclosporine therapy. His renal function remained stable. He responded to chemotherapy initially, but this response was short. Ten patients with renal transplants and cancer who were treated with cisplatin have been reported previously. Two were maintained on cyclosporine for immunosuppression throughout chemotherapy. No patient developed renal failure during or shortly after administration of cisplatin. Two of five patients treated for testicular cancer developed renal failure at 3 and 6 years after completion of chemotherapy. However, in both cases the cause of renal failure was attributed to chronic rejection of the transplanted kidney. CONCLUSION: Renal transplant recipients usually tolerate cisplatin-based chemotherapy well. It should be offered to patients with potentially curable cancer (e.g., germ cell tumor). This case and a review of the literature suggest that these patients retain baseline renal function even if cisplatin-based chemotherapy and cyclosporine are given simultaneously.

Adult↗
PubMed1996

A dose-response study of the effect of flutamide on benign prostatic hyperplasia: results of a multicenter study.

OBJECTIVES: The objective of this study was to evaluate efficacy, safety, and dose-response profiles of four dosing schemes of flutamide over 24 weeks. METHODS: Patients were randomized to receive one of the following five treatment regimens for a period of 24 weeks: placebo capsule, flutamide capsules 125 mg twice daily, 250 mg once daily, 250 mg twice daily, and 250 mg three times daily. Patients were then evaluated at baseline (0 weeks) and at 4, 6, 12, 18, and 24 weeks after the start of treatment, and 8 weeks after the end of treatment (32 weeks). Evaluation of efficacy was performed by noting changes in urine flow rate, residual urine volume, symptom score, prostate volume, and prostate-specific antigen level. A total of 372 patients were enrolled into the study at 32 centers (14 centers in the United States and 18 international centers). RESULTS: Baseline peak urinary flow rate and percent change from baseline in maximum flow rate showed a dose-related increase at 4 and 6 weeks; this increase was significant in the 250 mg three times daily group. At later time points, no significant differences between the flutamide and placebo groups were observed, largely because of the decreasing number of evaluable patients. At 4 and 6 weeks, 25% of patients in the 250 mg three times daily group had more than 3 cc/s increase in uroflow compared to about 10% of placebo patients (P < 0.05). All flutamide-treated groups had a significant decrease in prostate volume from baseline to the last treatment visit compared to placebo and this reduction was dose related (in comparison to placebo: P < 0.05 for 125 mg twice daily and P < 0.001 for all other treatment arms). Median decrease for the flutamide-treated groups ranged from 6% to 23% at 12 weeks and from 14% to 29% at 24 weeks. All treatment groups showed a subsequent increase in prostate volume after treatment was stopped. Furthermore, there was a significant reduction in residual urine volume at 24 weeks only in the 250 mg three times daily group. It increased following cessation of therapy. Urinary symptoms at 6, 12, 18, and 24 weeks did not show any significant difference between placebo and any flutamide dose group. The most common adverse events were nipple and breast tenderness (42% to 52%), diarrhea (29% to 34%), and gynecomastia (14% to 19%). Each of these adverse events had a significantly higher incidence in all flutamide dose groups compared with placebo, but none appeared to occur in a dose-related fashion. Sixteen percent of patients in the placebo group and 25% to 39% of patients in flutamide groups were discontinued due to diarrhea (12% to 17%) or nipple and breast tenderness (4% to 8%). A total of 1% to 3% of patients in various treatment arms discontinued due to deranged liver enzymes (1% for placebo); and 1% to 4% due to impotence (1% for placebo). CONCLUSIONS: Flutamide reduced the prostate volume in a dose-related fashion and resulted in an increase in peak flow rate at 4 weeks (3% for 250 mg three times daily, P value < 0.05), but the early positive effects did not maintain statistical significance due to an increasing number of dropouts due to adverse events. Effect on postvoid residual volume was observed only at the highest dose and at 24 weeks (median reduction, 23 mL, P < 0.05). Despite volume reduction and early improvement in peak flow rate, there were no significant differences in urinary symptoms among the placebo and flutamide groups. Higher incidences of diarrhea, breast tenderness, and gynecomastia, however, were the main limiting factors in this study and until these problems are overcome, the role of flutamide in the management of benign prostatic hyperplasia remains investigational.

Aged↗
PubMed1996

Progressive myoclonus epilepsy EPM1 locus maps to a 175-kb interval in distal 21q.

The EPM1 locus responsible for progressive myoclonus epilepsy of Unverricht-Lundborg type (MIM 254800) maps to a region in distal chromosome 21q where positional cloning has been hampered by the lack of physical and genetic mapping resolution. We here report the use of a recently constituted contig of cosmid, BAC, and P1 clones that allowed new polymorphic markers to be positioned. These were typed in 53 unrelated disease families from an isolated Finnish population in which a putative single ancestral EPM1 mutation has segregated for an estimated 100 generations. By thus exploiting historical recombinations in haplotype analysis, EPM1 could be assigned to the approximately 175-kb interval between the markers D21S2040 and D21S1259.

Adult↗
PubMed1995

Computerized interactive morphometry in the differential diagnosis of irradiated prostates.

Radiation therapy is becoming a treatment of choice for many patients with prostatic carcinoma. Distinguishing radiation change in prostate glands from carcinoma may be difficult. In this study we objectively assessed, by morphometric methods, the nuclear characteristics of benign and malignant prostates with a history of radiation treatment (125I implant with or without prior external beam radiation). This is part of our continuing efforts to achieve difficult differential diagnoses by analyzing perimeter, diameter and nuclear profile area of cells or interest and applying methods of statistical classification. Biopsies were performed 18-36 months following implant therapy. Eleven cases with residual prostate tumor constituted the malignant group. These were compared to 20 benign cases (benign glands in the 11 carcinoma cases plus 9 other cases with no residual carcinoma). Immunohistochemical staining with keratin 903 was performed on all cases. Differences in the nuclear parameters were most evident in the average nuclear profile areas (32.5 microns 2 for the malignant groups vs. 39.6 for the benign) and in the mean maximal cord length (diameter) (7.4 microns for the malignant group vs. 9.0 for the benign). Classification, however, is based on the size distribution plots of nuclear profile areas, which, in the malignant cases, had a sharper peak at lower value, while the benign cases had higher value and a broader peak with a trailing off into the larger values. This study emphasized the marked nuclear alterations that occur in irradiated prostates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

Similar peptides from two beta cell autoantigens, proinsulin and glutamic acid decarboxylase, stimulate T cells of individuals at risk for insulin-dependent diabetes.

BACKGROUND: Insulin (1) and glutamic acid decarboxylase (GAD) (2) are both autoantigens in insulin-dependent diabetes mellitus (IDDM), but no molecular mechanism has been proposed for their association. We have identified a 13 amino acid peptide of proinsulin (amino acids 24-36) that bears marked similarity to a peptide of GAD65 (amino acids 506-518) (G. Rudy, unpublished). In order to test the hypothesis that this region of similarity is implicated in the pathogenesis of IDDM, we assayed T cell reactivity to these two peptides in subjects at risk for IDDM. MATERIALS AND METHODS: Subjects at risk for IDDM were islet cell antibody (ICA)-positive, first degree relatives of people with insulin-dependent diabetes. Peripheral blood mononuclear cells from 10 pairs of at-risk and HLA-DR matched control subjects were tested in an in vitro proliferation assay. RESULTS: Reactivity to both proinsulin and GAD peptides was significantly greater among at-risk subjects than controls (proinsulin; p < 0.008; GAD; p < 0.018). In contrast to reactivity to the GAD peptide, reactivity to the proinsulin peptide was almost entirely confined to the at-risk subjects. CONCLUSIONS: This is the first demonstration of T cell reactivity to a proinsulin-specific peptide. In addition, it is the first example of reactivity to a minimal peptide region shared between two human autoimmune disease-associated self antigens. Mimicry between these similar peptides may provide a molecular basis for the conjoint autoantigenicity of proinsulin and GAD in IDDM.

Adolescent↗
PubMed1994

Conservative treatment of type III renal trauma.

Type III renal injuries, deep cortical lacerations with or without urinary extravasation, have traditionally been managed by exploration and surgical repair. With improved and readily available radiologic imaging modalities such as computed tomography and intravenous pyelography, we propose that the majority of these injuries can be followed expectantly with delayed intervention as needed. The records of 71 patients with both blunt abdominal and penetrating trauma with suspected significant renal injuries were reviewed. Eighteen patients (nine blunt and nine penetrating trauma) with type III injury were identified. Thirteen patients had their renal injuries treated conservatively and three patients underwent immediate surgical repair. Two patients died of associated injuries shortly after arrival at the emergency room. Two of the conservatively treated patients and one who had initial repair needed subsequent intervention, but no renal unit was lost because of delayed intervention. Thus, of the 16 surviving patients with type III injuries, 13 (81%) were successfully managed conservatively without the need for surgical intervention. With the aid of computed tomography, conservative therapy for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss.

Adult↗
PubMed1993

Parental abuse as a precursor to childhood onset depression and suicidality.

Child guidance clinic cases were reviewed for abuse history, diagnosis, depressive symptoms, and suicidality. Many depressed abused children were found to have been previously diagnosed exclusively with conduct-related versus affect disorders. The results suggested that abused children are at specific risk of developing depression and suicidality and that a subgroup of those with early-onset depression may have acquired the disorder concurrent with parental abuse.

Adolescent↗
PubMed1992

Protein kinases from Aspergillus nidulans that phosphorylate the carboxyl-terminal domain of the largest subunit of RNA polymerase II.

Three serine kinases which phosphorylate the CTD of RNA polymerase II have been identified in Aspergillus nidulans. The kinases (KI, KII, KIII) were identified using a synthetic peptide containing four copies of the CTD consensus heptamer repeat, and differ in chromatographic behavior, and apparent molecular mass (KI approximately 60kDa; KII approximately 82kDa; KIII approximately 43 kDa). KIII utilized, in addition to peptide, histone H1 as substrate, whereas casein was not phosphorylated by any of the three kinases. The kinases appear to be unrelated to the p34cdc2 kinase, as judged by Western blot analysis and the position of serine phosphorylation of the synthetic CTD peptide. KI was highly purified and renaturation experiments have shown that it consists of a single polypeptide of 57 kDa. KI also phosphorylated RNA polymerase II associated in a preinitiation complex.

Amino Acid Sequence↗
PubMed1992

Laparoscopy for evaluation of cryptorchid testis.

Four male patients with a unilateral nonpalpable testis were considered for laparoscopy. Preoperative evaluation by computerized tomography and ultrasonography failed to demonstrate cryptorchid testis. Laparoscopy clearly identified the anatomy in all 4 cases. Two patients had an absent testis, 1 patient underwent orchiectomy for a dysmorphic testis, and 1 patients underwent orchiopexy for a testis located within the inguinal canal. Pediatric laparoscopy is an effective and safe adjunct in the management of cryptorchid testis.

Adult↗
PubMed1991

Value of serum alkaline phosphatase and radionuclide bone scans in patients with renal cell carcinoma.

Ninety-one patients who underwent radical nephrectomy for renal cell carcinoma (RCC) were reviewed to determine the prognostic value of serum alkaline phosphatase (SAP) levels and radionuclide bone scan. A preoperative SAP greater than 127 IU/L was a strong indicator of eventual disease progression or death, and an elevated SAP was a better predictor of eventual outcome than bone scan.

Alkaline Phosphatase↗
PubMed1990

Persistent abnormalities in lipoprotein composition and cholesteryl ester transfer following lovastatin treatment.

Optimally effective lipid-lowering agents should not only restore plasma lipids to normal levels but also correct potentially atherogenic alterations in lipoprotein composition and function often present in hyperlipidemic patients. Lovastatin, a competitive inhibitor of cholesterol biosynthesis, clearly lowers plasma cholesterol levels. Its effects on lipoprotein composition and cholesteryl ester transfer (CET), a key step in reverse cholesterol transport, however, are not known. Since abnormalities in CET and lipoprotein composition are present in patients with hypercholesterolemia, we studied these parameters of plasma lipoprotein transport in twelve hypercholesterolemic (HC; Type IIa) subjects (six male, six female) before and 2 months after lovastatin treatment (20 mg qd). Before lovastatin, the free cholesterol (FC)/lecithin (L) ratio in plasma, a new index of cardiovascular risk that reflects lipoprotein surface composition, was abnormally increased (1.18 +/- 0.26 vs controls 0.83 +/- 0.14; P less than 0.001) in very low density lipoproteins (VLDL) and high density lipoprotein-3 (HDL3), and remained so after treatment despite significant declines in whole plasma cholesterol (311.7 +/- 68.2 vs 215.6 +/- 27.2 mg/dl; P less than 0.001), low density lipoprotein (LDL)-cholesterol (206.3 +/- 47.9 vs 146.8 +/- 29.4; P less than 0.001), and apolipoprotein B (149 +/- 30 vs 110 +/- 17; P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The adenovirus inverted terminal repeat functions as an enhancer in a cell-free system.

Two binding sites for EivF, a factor involved in transcription from the adenovirus early promoter iv (Eiv), were mapped within the adenovirus inverted terminal repeats (ITR). Consistent with the observation that EivF was required to initiate transcription from the Eiv promoter and with the demonstration that two EivF binding sites were present in the ITR, we show that the inverted terminal repeat region was able to promote transcription from the CAP site of the Eiv promoter in vitro and in an EIa-dependent fashion in vivo. The minimum sequence within the ITR capable of directing EIa-dependent transcription consists of forty nine nucleotides comprising two EivF binding sites and at least one Sp1 binding site. This 49-base pair fragment possesses the characteristics of an enhancer which is induced by EIa. The enhancer is active in HeLa cell nuclear extracts. Transcription directed by the ITR required EivF and the general transcription factors. The addition of purified Sp1 factor specifically stimulated transcription which correlates with the presence of Sp1 binding sites between the two EivF recognition sites.

Adenoviridae↗
PubMed1989

Interaction between cortisol and microbial proteases.

Binding (or interaction) of cortisol with microbial molecule(s) was observed by employing Bio-Gel HTP affinity chromatography and subsequently by fluorescence spectrophotometry. Molecule(s) in the crude extract of baker's yeast and in other microbial proteases exhibited varied degrees of cortisol-binding. Bacterial protease (type IX) had highest, while the type XXVI enzyme had the lowest, binding capacity. In addition, these two proteases exhibited a distinct difference in the alterations of ultraviolet spectra due to interaction with cortisol. Using casein as a substrate, cortisol, CTP, trypsin inhibitor or leupeptin appreciably inhibited type IX protease at low concentrations of Ca2+. However, thyroxine had no effect on this protease.

Bacteria↗
PubMed1987

Amyotrophic lateral sclerosis: a challenge for constant adaptation.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor disease of unknown etiology with insidious onset and a progressive course. It interferes with a wide variety of patient motor activities, which may include those controlled by the lower cranial nerves--swallowing, speech, and respiration. Many health professionals should be involved early on to maintain an optimal quality of life for the patient and family. When possible, other supportive patients, families, and ALS groups should be contacted for emotional support and practical information. Nursing care should be adaptive, and the confidence of the patient maintained in a variety of settings. Research about ALS is often of vital interest to patients and may give them a purpose for living and hope for ultimate benefit to others. Final decisions regarding care should be made by the patient and his primary caregiver.

Adaptation, Psychological↗