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Biomedical subjects

A Malkin

Publications and source records attributed to A Malkin.

At least 19 recordsLinked to original sources
PubMed2005

Comparison of DNA extraction from cervical cells collected in PreservCyt solution for the amplification of Chlamydia trachomatis.

OBJECTIVE: The aim of this study was to compare and evaluate three methods of DNA extraction for the amplification of Chlamydia trachomatis in uterine cervical samples collected in PreservCyt solution. ThinPrep is the trade name for the slide preparation. METHODS: Thirty-eight samples collected in LCx buffer medium, which were identified as C. trachomatis infected by ligase chain reaction (LCR), were selected for this study. DNA from the PreservCyt samples was extracted by three methods: (i) QIAamp kit, (ii) boiling in Tris-EDTA buffer with Chelex purification, and (iii) Proteinase K digestion with Chelex purification. Sample DNA was tested for the presence of C. trachomatis by PCR using cryptic plasmid research (CTP) primers and major outer membrane protein research momp gene (MOMP) primers. Real-time (LightCycler) PCR for relative C. trachomatis quantification following DNA extraction was performed using primers (Hsp 60) for the 60 kDa heat-shock protein hsp60 gene. RESULTS: Amplification using CTP primers was the most successful with each of the extraction protocols. Boiling in buffer was the least successful extraction method. QIAamp was the best extraction method, yielding the most positives with both the CTP and MOMP primers. Proteinase K-Chelex extraction gave similar sensitivity to QIAamp extraction with CTP primers but lower for MOMP primers. CONCLUSIONS: The DNA extraction method must be carefully selected to ensure that larger PCR amplicons can be successfully produced by PCR and to ensure high sensitivity of detection of C. trachomatis. In this study it was found that the QIAamp extraction method followed by PCR with the CTP primers was the most successful for amplification of C. trachomatis DNA.

Antigens, Bacterial↗
PubMed2002

Evaluation of liquid-based cytology in cervical screening of high-risk populations: a split study of colposcopy and genito-urinary medicine populations.

A split study evaluated the ThinPrep(R) PapTesttrade mark (TP; Cytyc Corp., Boxborough, MA) compared with current methodologies of cervical cytology in two high-risk cohorts. One thousand, three hundred cases from a colposcopy clinic and a genito-urinary medicine outpatient clinic were examined. The TP reported increased detection of all grades of dyskaryosis (mild, moderate and severe; + 4.5%) and a decrease in borderline and unsuitable cases (- 4.9%). Four cases of high-grade dyskaryosis (moderate or severe) were detected only using the TP, while an additional four cases classified as high-grade dyskaryosis with the TP were reported as borderline by our conventional methods. The split-study finding of increased sensitivity with the TP provides for improved clinical management of patients in our high-risk cohorts.

Cell Nucleus↗
PubMed2001

A comparative study: conventional preparation and ThinPrep 2000 in respiratory cytology.

In order to compare and contrast conventional preparation (CP) with ThinPrep 2000 (TP) in respiratory cytology, 207 samples were divided equally and processed by the two different preparation methods, generating three CP and one TP slide per sample. No lesion identified by CP was missed by TP and there were no significant differences between TP and CP in the diagnostic categories. However, two cases of squamous cell carcinoma were detected on TP which had been classified as unsatisfactory and moderate squamous dyskaryosis, respectively, on CP. ThinPrep was found to be superior to CP in many respects as it provided standardized preparations in a greater proportion of cases and problems such as cell overlapping and background debris were markedly reduced. In several instances the diagnostic accuracy in CP was compromised by smears that were either too thick, too thin, or too scanty. Cell preservation was also better on TP when compared with CP, facilitating more accurate diagnosis and significantly reducing the primary screening and reporting time, especially of sputum samples. A major advantage of TP methodology is the fact that it facilitates optimal use of skilled cytotechnologists and streamlines the workflow in the laboratory.

Carcinoma↗
PubMed1993

An epidemiologic study of hemorrhagic fever with renal syndrome in Bashkirtostan (Russia) and Sweden.

The incidence and antibody prevalence of hemorrhagic fever with renal syndrome (HFRS) in Bashkirtostan (European part of Russia) and northern Sweden was compared with the abundance of Clethrionomys glareolus (bank voles) in the two areas. In Bashkirtostan, 10% of the women and 15% of the men were found to be antibody positive. The corresponding figures for Sweden were 8% and 16% for women and men, respectively. The annual incidence of HFRS in Bashkirtostan was 50 cases per 100,000 inhabitants, with a male:female ratio of 4.6:1. The incidence in the endemic area of Sweden was seven cases per 100,000 inhabitants, with a male:female ratio of 1.8:1. A similar age distribution of cases, with a peak in the middle age groups, especially in men, was found in both Bashkirtostan and Sweden. The incidence of HFRS in humans and the abundance of bank voles varied with time in both Bashkirtostan and Sweden, but the study failed to find any significant correlation between the two variables. The study showed that HFRS causes significant human morbidity in the areas studied but that both incidence and possibly bank vole abundance was higher in Bashkirtostan than in northern Sweden.

Adolescent↗
PubMed1992

Changes in thyroid hormones, thyroid stimulating hormone and cortisol in acute spinal cord injury.

To determine the hormonal response to acute spinal cord injury, serial serum samples were collected from 18 patients with acute spinal cord injury and from 14 control patients with spinal fractures without cord injury. The first sample was taken within 24 hours of injury, the second at 24-48 hours; and the third at 7 days for determination of thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), T3 uptake (T3U), thyroid stimulating hormone (TSH), thyroxine binding globulin (TBG), growth hormone (GH), cortisol, and insulin. Significant increases were observed in rT3 levels and transient changes were observed in the T4 and T3 levels in the spinal cord injured group but not in the group with spinal fractures alone. The changes in the spinal cord injured patients are consistent with the 'low T3 syndrome'. However, the persisting rise of rT3 at 7 days was an unexpected finding. In addition to the cord injury, these changes may also be related to dexamthasone administration and nutritional factors.

Acute Disease↗
PubMed1991

Effect of anticoagulants in vitro on the viability of lymphocytes and content of free fatty acids in plasma.

These authors attempted to test the effect of anticoagulants on lymphocytes viability by reproducing the procedure used for lymphocyte isolation for various immunologic tests in which blood specimens are allowed to stay at room temperature for 2 h before lymphocytes are isolated. Blood was obtained with three different anticoagulants i.e. heparin, citrate, and CPDA (citrate, phosphate, dextrose, and adenine). Plasma was lyophilized and extracted with ethanol. Dried ethanol extracts were suspended in medium (RPMI 1640 + 10% fetal bovine serum) and incubated with a lymphocyte cell line (MOLT-4). After 24 h of incubation the viability of cells was examined. The following death rates of the cells were observed: heparin -63 +/- 4.6% (mean +/- SEM), citrate -27 +/- 6.7%, and CPDA 6.2 +/- 0.6% (P less than 0.0005). A significant correlation was found between these results and changes in the concentrations of free fatty acids in the extracts. These results emphasize the importance of choosing the right anticoagulant when the viability of lymphocytes is obligatory.

Adenine↗
PubMed1991

An assessment of combined tumour markers in patients with seminoma: placental alkaline phosphatase (PLAP), lactate dehydrogenase (LD) and beta human chorionic gonadotrophin (beta HCG).

We have assessed the tumour markers placental alkaline phosphatase (PLAP), lactate dehydrogenase (LD), and human chorionic gonadotrophin (beta HCG) using 2,000 serum samples from 286 patients with seminoma. The ROC curves show that no one marker performs adequately for the detection of disease either at initial staging or during follow-up. We used a Markov model heuristically to devise strategies, in which marker results were assessed in combination, which might be useful in clinical practice. We found that the best strategy was to consider a test result abnormal only if either the beta HCG was greater than 6 Ul-1 or the LD was greater than 400 U l-1 and the PLAP level was greater than 60 U l-1. This will detect about 50% of patients with disease and the false-positive rate is 2%. In practical terms this means that PLAP need only be estimated in patients whose beta HCG is less than 6 IU l-1 and whose LD is greater than 400 U l-1.

Alkaline Phosphatase↗
PubMed1991

Nocturnal cortisol, thyroid stimulating hormone, and growth hormone secretory profiles in depressed adolescents.

Twelve depressed adolescents and 12 controls matched for age, sex, Tanner stage, time of menstrual cycle (females), weight, and time of year assessed were studied over 3 nights. Measurements for cortisol, thyroid stimulating hormone, and growth hormone were made on serum collected at 10 P.M., 12 midnight, 1 A.M., 2 A.M., 3 A.M., 4 A.M., and 6 A.M. in eight pairs and every 20 minutes from 8 P.M. to 7 A.M. in four pairs. Cortisol secretion did not significantly differentiate the groups. Thyroid stimulating hormone secretion was significantly elevated in the depressed group at one time point. Growth hormone secretion significantly differentiated the two groups at most time points, and the depressed adolescents significantly hypersecreted growth hormone (area under the curve). Implications for the diagnosis, etiology, and treatment of adolescent depression are discussed.

Adolescent↗
PubMed1991

Circulating arginine-vasopressin, calcitonin, carcinoembryonic antigen, neuron-specific enolase, and beta-2 microglobulin fluctuations during combined modality induction therapy for small-cell bronchogenic carcinoma. Association of postchemotherapy AVP surge with high tumor response rate and durable remission.

While on combined modality induction therapy, 88 small-cell lung cancer (SCLC) patients were studied longitudinally for changes in circulating tumor-associated substances (TAS). Chemotherapy protocols were CAV (cyclophosphamide, doxorubicin, vincristine), PE (cisplatin, etoposide), sequential CAV greater than PE and alternate CAV/PE. Sixty patients were given prophylactic cranial irradiation (PCI) and 40 remitting patients were irradiated to the primary thoracic tumor. Of 73 evaluable patients, 43 had blood sampling adequate for analysis of treatment-related TAS fluctuations. Fourteen patients demonstrated 16 events of transient arginine-vasopressin surge following chemotherapy. In decreasing order of frequency, the surge occurred after the first (9), second (6) and third (1 event) course of chemotherapy. Three patients had a concomitant increase of one of the following markers: carcinoembryonic antigen (CEA), calcitonin and neuron-specific enolase. Another patient showed an exclusive CEA surge. This group of patients (10 with limited, 4 with extensive disease) had a 93% objective response rate (57% complete, 36% partial) with a median duration of 9 months and a survival of 15 months. Five other patients, 2 with limited and 3 with extensive disease, showed a TAS surge after PCI. Their response was complete in 1 (8 months' duration) and partial in 3 cases (2, 4 and 4 months' duration, respectively) with a median survival lasting only 8 months. This study suggests that a chemotherapy-related TAS surge may be an early indicator of a favorable tumor response in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer.

Pretreatment serum lactate dehydrogenase (LDH) levels were assayed in 288 patients presenting with small-cell lung cancer (SCLC) between 1976 and 1985. Patients were routinely staged by physical examination, chest x-ray, bone, brain, and liver scans, and bone marrow evaluation. Clinical response and survival were assessed following treatment with combination chemotherapy as part of four clinical trials. Patients with extensive disease (ED) presented with a higher incidence (108 of 147, 73%) of abnormally elevated LDH (greater than 193 IU/L) than those (65 of 141, 46%) with limited disease (LD) (P = 2 x 10(-6)). Forty percent of patients had an initial normal LDH level and a higher response rate (89 of 108, 82%; complete response [CR], 47%) than those with elevated values of LDH (119 of 156, 76%; CR, 29%). The CR rate varied inversely with the level of LDH in patients with LD (P = .026) but not in those with ED (P = .300). The median survival time and 1-year and 2-year survival rates for patients with elevated LDH were 39 weeks and 33% and 6%, respectively, whereas for those with a normal LDH level these were 53 weeks and 54% and 16%, respectively. Patients with LD and elevated levels of LDH manifested a higher relative death rate (1.63:1) when compared with patients with LD and LDH in the normal range (P = .0083). The survival of patients with ED did not differ between those with normal and elevated levels of LDH (P = .273). A significant survival advantage persisted for patients with LDH in the normal range following adjustments for extent of disease, performance status (PS), and treatment protocol (P = .044, log-rank analysis). In conclusion, serum LDH appears to be a significant independent pretreatment prognostic factor in patients with SCLC that correlates with stage of disease, response to treatment, and survival.

Adult↗
PubMed1990

Is placental alkaline phosphatase (PLAP) a useful marker for seminoma?

The usefulness of placental alkaline phosphatase (PLAP) as a tumour marker was assessed in 1578 serum samples from 236 patients with seminoma. Smoking habits were known for all but 7 patients (22 samples). Smoking was associated with significantly higher mean levels of PLAP in disease-free patients (28.8 [S.E. 2.1] U/l vs. 15.9 [1.3] U/l in non-smokers). Mean PLAP levels were higher in patients with active disease (78.6 [23.5] U/l in non-smokers and 47.2 [18.5] U/l in smokers). The median values showed a similar trend. However, there was considerable overlap between the various groups and differences between mean and median values indicated that PLAP values were distributed asymmetrically. The predictive value of PLAP as a tumour marker was consequently much less than superficial inspection of these values might suggest. In 97 patients on surveillance, only 2 out of 11 patients who relapsed had elevated PLAP at the time of clinically detectable relapse. With the upper limit of normal PLAP quoted by our laboratory (35 U/l), specificity and sensitivity were, respectively, 88% and 45% (all patients) and 96% and 47% (non-smokers). The sensitivity and specificity of PLAP were assessed in more detail for a series of threshold values (normal vs. abnormal) with a graphical method. Only in non-smokers did PLAP seem useful and even in this group the positive predictive value of an "abnormal" test may be low; less than 50% in clinically relevant circumstances. Serum PLAP assay cannot usefully stand alone as a marker for seminoma and its routine estimation contributes little to follow-up.

Adult↗
PubMed1990

The effect of HIV-1 infection on the lipid fatty acid content in the membrane of cultured lymphocytes.

Elevations in the levels of unsaturated fatty acids (FAs) in membrane lipids lead to an increase in cell membrane fluidity and may also be involved in cell fusion and death through the loss of normal membrane function and integrity. Since the infection of susceptible cells with HIV leads to cell fusion and subsequent loss of viability, the present study was undertaken to see whether HIV infection can alter the relative content of unsaturated FAs in the host cell membrane and to determine whether this change correlates with cell death. Peripheral lymphocytes (PBLs) of a healthy donor and two CD4+ cell lines were chosen: MT-4, which is killed following HIV infection, with significant cell death being observed 5 days postinfection, and H9 which is not killed. Measurements of FA content of the two cell lines and PBLs, either before or at 6, 24, and 48 h after infection, showed a significant rise in the concentration of unsaturated FAs followed by a drop in the concentration of saturated FAs in the MT-4 cell line. With regard to the H9 cell line similar results were obtained at 6 h from infection. However, at 24 and 48 h the concentrations of saturated FAs returned to preinfection levels while the concentrations of unsaturated FAs dropped to levels even lower than those obtained at zero time. No significant changes in FA composition were found with PBLs.

CD4-Positive T-Lymphocytes↗
PubMed1990

Cortisol catabolism by lymphocytes of patients with chronic lymphocytic leukemia.

A low rate of catabolism of cortisol by lymphocytes correlates with high sensitivity of the cells to the steroid and causes them to die at a greater rate than control samples. Since lymphocytes of patients with chronic lymphocytic leukemia respond to treatment with glucocorticosteroids and are cortisol sensitive, we attempted to see whether their capability to catabolize cortisol differs from that of normal lymphocytes. No difference was found between the two groups of cells with regard to the pattern of cortisol metabolites. However, the lymphocytes of the chronic lymphocytic leukemia groups showed a total cortisol catabolism per cell that was significantly lower than that of the control group. Patients with low lymphocyte count in peripheral blood showed a relatively higher cortisol metabolism by lymphocytes per cell than those with high counts.

B-Lymphocytes↗
PubMed1990

Cortisol catabolism by lymphocytes of patients with systemic lupus erythematosus and rheumatoid arthritis.

We have shown that low cortisol catabolism by lymphocytes correlates with a high sensitivity of the cells to the steroid. In the present study, we aimed to assess whether high resistance to corticosteroid treatment correlates with a high rate of cortisol catabolism by lymphocytes. Since patients with systemic lupus erythematosus (SLE) usually require high doses of corticosteroids, while patients with rheumatoid arthritis (RA) respond to relatively low doses of steroids, we compared the capability of lymphocytes of patients with SLE and RA to catabolize cortisol. The rate of cortisol catabolism obtained with the RA group was not significantly different from that obtained with the control group. The catabolism of cortisol by lymphocytes of the SLE group was significantly higher than both the control group (p less than 0.05) and the RA group (p less than 0.01). A significant correlation was demonstrated between the SLE disease activity index and rates of cortisol catabolism attained by lymphocytes of SLE patients (p less than 0.001).

Adrenal Cortex Hormones↗
PubMed1989

The effect of fatty acids on the vulnerability of lymphocytes to cortisol.

We have shown previously that cortisol-sensitive lymphocytes (thymocytes) have a much lower capacity than cortisol-resistant cells to catabolize cortisol and that linoleic acid inhibits the catabolism of cortisol by lymphocytes and modulates the sensitivity of lymphocytes to cortisol. In the present study, we attempted to see whether other fatty acids are inhibitory and if inhibition of cortisol catabolism by lymphocytes indicates a change in resistance of the cells to cortisol. Measuring the effect of fatty acids on cortisol catabolism by lymphocytes indicated that the polyunsaturated fatty acids, linoleate, arachidonate, and eicosapentaenoic, inhibit cortisol catabolism by lymphocytes. Using prostaglandin PGE2 and indomethacin as a blocker of prostaglandin formation, we observed that the effect of the polyunsaturated fatty acids was not due to the formation of prostaglandins. Examining the effect of fatty acids on the vulnerability of lymphocytes to cortisol, we noted that saturated fatty acids had no significant effect, whereas the aforementioned polyunsaturated fatty acids make lymphocytes more sensitive to cortisol.

Arachidonic Acid↗
PubMed1989

Albumin and the unique pattern of inhibitors of cortisol catabolism by lymphocytes in serum of cancer patients.

We have shown previously that sera of cancer patients (CPS) possess ethanol-extractable substances which can inhibit the catabolism of cortisol by lymphocytes (CCL). In the present study an attempt was made to purify the inhibitory material by gel filtration. Chromatography of normal serum and CPS on a Sephadex G-10 column showed one peak of CCL inhibition with control serum and two peaks with CPS. The one peak which was common to both sera appeared with the void volume and was identified as albumin. The second peak which was present with CPS only, appeared at a molecular weight range of 300-350 daltons. We postulate that CPS may contain a relatively high concentrations of small molecules which are not bound to proteins and which might modulate the normal function of the immune system.

Chromatography, Gel↗
PubMed1989

Carcinoembryonic antigen, arginine vasopressin and calcitonin as markers of early small-cell lung cancer relapse.

Patients with small-cell lung cancer (SCLC) underwent serial blood monitoring during remission: 66 were tested for carcinoembryonic antigen (CEA) and calcitonin (CTN), including 40 who were concomitantly tested for arginine vasopression (AVP) as well. 83% of the patients had at least one assay elevated prior to induction therapy. By serial monitoring, blood concentrations reflected disease course and reached lowest levels at remission. CEA, AVP and CTN shifted along the course of disease independently of each other; a normal pretreatment titer did not preclude its rise at a later phase, while an initially elevated assay could normalize at remission and stay normal thereafter. The median lead time (LT) to clinically diagnosed relapse, for limited-disease patients, was 229 days for complete and 90 days for partial remitters. Patients with extensive disease had similar LT values. LT to local recurrence was shorter than to distant relapse. Remission AVP titers of up to 6 ng/ml conferred disease-free survival (DFS) longer than that associated with higher titers (median DFS 518 vs. 211 days, respectively; p = 0.045 for curve differences). The relative risk (RR) of relapse associated with pretreatment patient characteristics and with absence or presence of tumor marker normalization at remission was estimated by the Cox proportional hazards model. This analysis revealed that the RR of relapse conferred by pretreatment attributes, e.g. disease extent, was considerably modified by biochemical co-variates at remission, e.g. serum CEA level relative to a 3 ng/ml cutoff point.

Arginine Vasopressin↗