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Biomedical subjects

G Zajicek

Publications and source records attributed to G Zajicek.

At least 19 recordsLinked to original sources
PubMed2001

Calcium supplements interact significantly with long-term diet while suppressing rectal epithelial proliferation of adenoma patients.

BACKGROUND: Calcium supplements to the western-style diet may reduce the risk for colorectal neoplasia. Using rectal epithelial proliferation (REP) measurements as a biomarker of response to intervention, the authors evaluated the effects of 1-year calcium supplementation in adenoma patients and its possible interactions with the patients' dietary and lifestyle habits. METHODS: Consenting adenoma patients, without a family history of colorectal neoplasia, were randomly selected to receive 3.75 g calcium carbonate (1.5 g Ca2+) daily or to receive no treatment. All had their long-term dietary and lifestyle habits assessed and their REP labeling index (LI) evaluated before and at end of follow-up. The change in LI was compared between groups, and statistical associations were examined between mean nutrient consumption and treatment effect and between lifestyle and treatment effect. RESULTS: Fifty-two adenoma patients (33 treated and 19 untreated) completed intervention and follow-up. There were no significant differences between study groups in age, weight, cigarette smoking, or medication use. The LI decreased in 58% of calcium-intervened patients and in only 26% of nonintervened patients (P = 0.04); the mean LI x 100 (+/- standard deviation) of the former fell from 5.04 +/- 1.93 to 4.54 +/- 1.58, and rose from 4.32 +/- 1.58 to 4.93 +/- 1.58 in the latter (P = 0.04). A lower fat, a higher carbohydrate, fiber, or fluid intake each interacted with the calcium supplementation to decrease the LI (P = 0.02, 0.001, 0.02, and 0.08, respectively). CONCLUSIONS: Long-term calcium supplements significantly suppressed REP in adenoma patients, and long-term dietary habits contributed to this effect. Patient diet should be assessed when researchers use REP as a biomarker in calcium chemoprevention studies. Study results indicated that relevant dietary counseling may be useful in addition to calcium supplements in persons at increased risk for colorectal neoplasia.

Adenoma↗
PubMed2001

Cancer and metaphysics.

Metaphysics, is generally a pleasant, and harmless intellectual endeavor. Even if leading to wrong conclusions, nobody is hurt. Suppose that contrary to general belief, the Big Bang (1) never happened and the world is eternal. No harm is done. Some philosophers, like Kant, enjoyed life despite the fact that, nature, or the thing in itself, eluded their understanding (2). But suppose that the thing in itself is your patient, and you apply metaphysical reasoning for his treatment, metaphysics may occasionally be damaging. This is particularly pertinent to cancer, a disease that is haunted by false metaphysical statements. Since cancer is part of medicine, the present discourse deals with medical metaphysics. Medicine provides a simple way, or rule of thumb, for distinguishing between correct and wrong medical metaphysical statements. If they harm the patient, they are wrong, and if they aid him, they are correct. Statements that do not affect a patient's well being, e.g., 'Big Bang may be hazardous to your health', are of no apparent value and doubtful. Since treatment outcome is generally uncertain, the physician continually searches for new ideas that may aid his patient, even if they are metaphysical. In diseases, like cancer, that elude his understanding, his adherence to metaphysics intensifies, and he is ready to consider even doubtful suggestions for treatment. Yet by relaxing the rules of thumb for evaluating metaphysical concepts, he gradually slips into the irrational domain.

Humans↗
PubMed2000

Computer assisted physiologic monitoring and stability assessment in vascular surgical patients undergoing general anesthesia--preliminary data.

BACKGROUND: Physiologic monitors present an influx of numerical data that can be overwhelming to the clinician. We combined several parameters in an effort to reduce the amount of information that must be continuously monitored including oxyhemoglobin saturation by pulse oximetry, end-tidal CO2 concentration, arterial blood pressure, and heart rate into an integrated measure--the health stability magnitude (HSM). The HSM is computed for a predetermined basal period, the reference HSM (RHSM), and recalculated continuously for comparison with the baseline value. In this study we present the HSM concept and examine changes in the HSM during abdominal aortic aneurysm surgery. MATERIALS AND METHODS: After IRB approval, nine patients were studied. The anesthesiologist recorded all significant intra-operative events. Within a defined time interval, data were recorded and used to calculate a combined parameter, the HSM. The baseline or reference value of this index (RHSM) was calculated after the induction of anesthesia. Individual HSM values were repeatedly calculated for ten second periods after the RHSM value was established. A > 30% deviation of the HSM from the RHSM was considered significant. Deviations in the HSM were compared with events recorded by the anesthesiologist on a paper record and with the record from an electronic record-keeping system. The deviation observed between two consecutive HSMs, called dHSM, was plotted against HSM to construct a contour diagram of data from all patients to which individual cases could be compared. RESULTS: The plot showed that dHSM vs. HSM values were tightly clustered. The inner contour on the distribution plot contained 90% of values. Individual patient's time course, projected on this diagram, revealed deviations form "normal" physiology. Fifty-nine events led to > 30% deviations in the HSM; 27 were anticipated events and 32 were unanticipated. CONCLUSION: The correlation between HSM and dHSM depicts changes in multiple monitored parameters that can be viewed using a single graphical representation. Projection of individual cases on the contour diagram may help the clinician to distinguish relative intraoperative stability from important events. Data reduction in this manner may guide clinical decision-making in response to unanticipated or unrecognized events.

Aged↗
PubMed1999

Similarity measurement method for the classification of architecturally differentiated images.

A similarity measurement method for the classification of architecturally differentiated image sections is described. The strength of the method is demonstrated by performing the complex task of assigning severity grading (Gleason grading) to histological slides of prostate cancer. As shown, all that is required to employ the method is a small set of preclassified images. The images can be real world images acquired by means of a camera, computer tomography, etc., or schematic drawings representing samples of different classes. The schematic option allows a quick test of the method for a particular classification problem.

Computers↗
PubMed1999

Wisdom of the body.

Modern medicine still fails to explain processes that operate in self-healing diseases. We may thus distinguish between two kinds of processes that operate in the body: explained and unexplained. The latter operate in self-healing diseases, and are either ignored by medicine or called placebos. Hippocrates regarded such processes as the healing force of nature and the task of the physician was to assist the healing force. The unexplained processes in physiology were defined by Starling and Cannon as Wisdom of the Body (WOB). This concept is applied here for a rational treatment of processes involved in health and in disease. WOB is an attribute of live organisms. It directs growing plants toward sunshine, guides amebas away from noxious agents, and determines the behavior of higher animals. It is essential for individual survival and was molded by natural selection. During evolution, WOB encountered all diseases, knows how to heal itself, and anticipates all diseases. The main task of the WOB is to maintain health, and improve its quality. It controls processes in the body so as to make them healthier. The WOB has its own language and should be considered when examining patients.

Brain↗
PubMed1998

Rectal epithelial proliferation in persons with or without a history of adenoma and its association with diet and lifestyle habits.

BACKGROUND: Rectal epithelial proliferation (REP) measurements are used as a biomarker of risk for colorectal neoplasia and response to chemoprevention. The authors evaluated REP in screenees with and without a history of adenoma and its association with demographic and adenoma characteristics, diet, and other lifestyle habits. METHODS: Long term lifestyle habits were evaluated and proliferation assessed by in vitro bromodeoxyuridine labeling of rectal biopsies in 223 screenees, 132 of whom had adenomas removed > 3 years previously. Analyses included the total population, screenees with a previous history of adenomas and adenoma free screenees separately, and a subgroup of 55 matched adenoma cases and controls. RESULTS: Crypt proliferation measurements were not elevated in screenees with a history of adenomas compared with adenoma free screenees (mean total labeling index [LI] of 4.8% and 4.9%, respectively). This was confirmed by the case-control analysis, in which the LI of the most superficial crypt compartment was lower in the adenoma cases (P=0.05). Moreover, their total LI correlated negatively with the number of adenomas removed previously (P < 0.01). Proliferation was more frequent in the most superficial crypt compartments of female adenoma free screenees than in female screenees with a history of adenomas (P=0.02), and in men age > 65 years compared with younger men (P=0.06). In the total population, negative Spearman rank correlations were found between total LI and long term dietary intake of calcium (correlation coefficient [r]=-0.15; P=0.02), LI of the two most superficial crypt compartments and intake of fiber (r=-0.18; P=0.01), water (r=-0.12; P=0.08), and carbohydrates (not significant). A positive correlation was found between LI of the most superficial crypt compartment and cigarette smoking (r=0.4; P=0.02). CONCLUSIONS: REP measurements did not discriminate between screenees with a history of adenomas and adenoma free screenees. Long-term lifestyle habits, gender, and age were associated with REP levels and need to be considered when evaluating human intervention studies.

Adenoma↗
PubMed1998

MIB-1 and PC-10 immunostaining for the assessment of proliferative activity in primary acquired melanosis without and with atypia.

AIMS: To compare the proliferative activity of intraepithelial melanocytes in primary acquired melanosis (PAM) without atypia and PAM with atypia by immunohistochemical staining for the Ki-67 antigen and the proliferating cell nuclear antigen (PCNA). METHODS: Formalin fixed, paraffin embedded sections from 35 archival specimens of PAM without atypia (n = 19) and with atypia (n = 16) were studied by immunostaining with MIB-1 and PC-10 monoclonal antibodies that react with the Ki-67 antigen and PCNA respectively. The results were calculated as the mean number of positive cells per eyepiece grid. All specimens were evaluated by two masked observers, and the interobserver reproducibility was assessed. RESULTS: The means of the positive cell count in PAM with atypia were significantly higher compared with PAM without atypia for both observers, in both the PC-10 and the MIB-1 stained sections. In a linear least square model that estimated the interobserver and between group variation, the difference of MIB-1 and PC-10 positive cell count between PAM without and with atypia remained highly significant. The difference between the observers was not significant. CONCLUSIONS: Immunostaining with MIB-1 and PC-10 demonstrated that PAM with atypia has higher proliferative activity than PAM without atypia. This method was found to be reproducible between different observers.

Antigens, Nuclear↗
PubMed1997

Methimazole slows hepatocyte streaming in rats.

Hepatocytes are hypothesized to continually stream from the portal tract to the terminal hepatic vein. By this model, when a cell divides, one of its progeny replaces the dividing ancestor and the other is displaced into a more remote location. The present experiment aims to demonstrate that hypothyroidism affects liver cell turnover. Thirty male adult rats were divided into two groups. One received methimazole for two weeks and the other served as control. Each rat was injected intraperitoneally with 18.5 KBq [3H]thymidine/g body weight. Rats were killed after 1 hr and two and four weeks. Autoradiography was done. The distance of the labeled cells from the portal tract was measured. The mean TSH levels of the methimazole-treated group and controls were 1.45 and 0.25 mM/liter, respectively (P < 0.01). Hepatocyte streaming was lower in hypothyroid (1.8 microns/day) than in untreated rats (2.5 microns/day) (P < 0.01). The respective labeling indices 1 hr after labeling were 0.9% and 1.24% (P < 0.05). We conclude that hypothyroidism diminishes hepatocyte and littoral cell turnover and slows down their streaming.

Animals↗
PubMed1996

Streaming conjunctiva.

BACKGROUND: Epithelial proliferation is linked with cell displacement. When a cell divides, one of its progeny replaces the dividing ancestor and the other is displaced into a more remote location that has to be vacated first by peripheral cells. As cells are neither pushed nor pulled in a mechanical sense, and since they do not move by their own means, this displacement is best regarded as streaming. The purpose of the present study was to measure epithelial cell streaming in adult rat conjunctiva. METHODS: Twenty-seven female adult rats were injected i.p. with 18.5 KBq [3H]-thymidine/g body weight, specific activity 185 GBq/mMol. Three rats were killed at different times up to 28 d. Eyes and eyelids were removed in one piece, cut along the pupillary-optic nerve line into 5-microns-thick sections, and prepared for autoradiography. In each eye, the entire upper conjunctiva extending from limbus to the palpebral muco-cutaneous junction was scanned with an ocular micrometer grid. The limbus served as point of origin. The x, y coordinate of each nucleus with two grains or more and its grain content were recorded. RESULTS: One hour after labeling, labeled cells were spread evenly along the basal layer. Cells of the upper layers were not labeled. As time passed by, labeled cells in the fornix became more abundant, while in the limbus and palpebral margin, their frequency declined. Labeled cells streamed from the limbus and palpebral muco-cutaneous junction to the fornix. Bulbar conjunctival epithelia streamed at a velocity of 13.2 microns/day. Epithelia in the palpebral conjunctiva streamed at a velocity of 11.8 microns/day. At the same time cells streamed from the basal layer to the epithelial surface at a velocity of 0.4 microns/day. Generation time was 3.9 days. CONCLUSIONS: Bulbar and palpebral conjunctivae are two independent cell kinetic systems that originate in two stem cell regions, one in the limbus and the other in the muco-cutaneous junction. Each system is made of two compartments, a progenitor where cells proliferate, and a compartment of non proliferating end cells. Progenitors created in the first, enter the second and turn into end cells. Ultimately they die in the fornix. The undetermined limbus stem cell generates two epithelial cell lines, a corneal and a conjunctival.

Animals↗
PubMed1996

Differing proliferative responses in proximal and distal colons of growing rats fed food eaten by adenoma patients.

Animal dietary studies related to human colorectal carcinogenesis are usually based on AIN-76A diet, which is dissimilar to human food in source, preparation, and content. Our aim was to examine colonic epithelial proliferation in rats fed a diet based on the mean daily food intake of adenoma patients. Foods were prepared as reported by the adenoma patients and dehydrated; 64 Sprague-Dawley rats were fed either "human adenoma" or AIN-76A diet and every eight weeks, eight from each group were sacrificed. Both groups gained weight equally, had no colonic histological changes, but during the study showed progressive lengthening of colonic crypts (P < 0.01) and decreased proliferation (P < 0.05) in distal colons. Compared to controls, rats fed human adenoma diet had significantly longer crypts (P < 0.01) and more labeled cells (P < 0.05) at 32 weeks; overall they had increased proliferation (P < 0.01), most significantly in the distal colon. Thus, food eaten by adenoma patients induced hyperproliferative changes in the rat colon during growth and maturity, especially the distal colon, as found in humans at risk for neoplasia.

Adenoma↗
PubMed1996

A new cancer hypothesis.

Despite intensive efforts to cure breast cancer, treatment generally fails, as evidenced by the age-adjusted mortality rate for breast cancer. For 60 years, breast cancer mortality remained virtually constant. As treatment failed to improve the life prospect of the average patient, it is based on false premises, e.g. Halsted's hypothesis, according to which the tumor is the only threat to the patient. Yet there is more to cancer than just the tumor. Two hallmarks of cancer, cachexia, and paraneoplasia, are usually ignored, since it is assumed that they are caused by the tumor. But what if it is the other way round, and cancer is first of all a cachexia accompanied by a tumor? At least this could explain why, in most cancers, treatment fails. Cancer is a chronic systemic disease with local manifestations like arteriosclerosis, which is also systemic and manifested solely by its local manifestations, e.g. stroke and myocardial infarction. In the same way as treatment of an ailing heart does not cure the underlying arteriosclerosis, tumor removal does not cure cancer, as it is 'metabolically' systemic. It is proposed here that carcinogens deplete a vital substance and induce a metabolic deficiency that ends in cachexia. In order to survive, the organism grows a protective organ-the tumor-that replenishes the missing substance. During the preclinical phase of cancer, deficiency is slight and compensated only by a minute tumor. With time, it gets worse and the tumor has to grow more and more in order to make up for the loss, causing pain and secondary damage to vital functions. The patient seeks help and the disease starts its clinical course. When deficiency worsens, the patient becomes cachectic and dies. Such a metabolic relationship exists in pernicious anemia, which illustrates how a tumor might be protective. Cancer is viewed here as pernicious cachexia induced by the loss of a vital metabolite and compensated by the tumor. Until the discovery of the missing substance, treatment ought to preserve the tumor and alleviate its secondary manifestations.

Breast Neoplasms↗
PubMed1996

Epithelial cell migration in the normal rat lens.

The purpose of the present study was to estimate the rate of the rat lens epithelium displacement. Twenty-four adult male rats were injected intraperitoneally with 18.5 kBq/g [3H] thymidine. Rats in groups of three were killed at the following times: after one hour, 3, 6, 9, 12, 15, 18 and 21 days. The enucleated eyes were fixed in formalin, embedded in paraffin, cut into 5 microns-thick sections, and subjected to autoradiography. The number of cells was counted, and the x-coordinate of each nucleus with three grains or more, and its grain content were recorded. Statistical analysis included analysis of variance and linear regression. The average lens diameter was 68 fields of 75 microns each (5.1 mm). Cell displacement was measured in two regions: Region A, the equatorial region, extending from field 0-20, and region B extending from field 20 to the lens center (field 34). Cells in region A are divided into two kinetic compartments, progenitor (P-cells) occupying fields 9-20, and non-proliferating (Q) cells occupying fields 0-8. Cells advanced from the P into the Q-compartment at a velocity of 21.8 microns/day. Cells did not move between field 20 and the lens center. These findings resemble kinetically renewing tissues, e.g. epidermis and crypt-villus in the gastrointestinal mucosa.

Animals↗
PubMed1996

The impact of endometrial preparation on implantation following cryopreserved-thawed-embryo transfer.

The efficacy of three protocols of endometrial preparation (spontaneous cycles, A: artificial preparation, B; ovarian stimulation, C) for cryopreserved-thawed human embryo transfer (CT-ET). The implantation and clinical pregnancy rates per cycle in 236 women undergoing 381 consecutive CT-ETs were evaluated according to the endometrial preparation protocol. No statistically significant difference was found in implantation rates per embryo transfer (A = 5.6%, B = 5.6%, C = 4.6%) and clinical pregnancy rates per cycle (A = 16.9%, B = 16.5%, C = 15.6%) between the three endometrial preparation protocols used. In conclusion, the specific method of endometrial preparation for CT-ET had no significant impact upon the implantation rate.

Adult↗
PubMed1995

Increased turnover of intrahepatic bile ducts induced by bromobenzene.

Intrahepatic bile duct epithelium consists of two kinetic compartments: a progenitor (P) and a functional (Q) compartment. Hitherto bromobenzene was known to poison only hepatocytes in the third acinus zone. The present experiment aims to demonstrate that bromobenzene affects also bile duct turnover. Thirty male adult rats received one intraperitoneal injection of bromobenzene and were sacrificed in groups of five at the following times: 1, 2, 3, 4, 7, and 14 days. They received [3H]thymidine 1 hr before sacrificing. Autoradiography was done. Bile ducts were evaluated in all portal tracts of the section. The number of epithelial cells in each duct cross section was counted and defined as bile duct class, which is roughly proportional to bile duct size. In each cross section the number of labeled cells was counted. Initially the labeling index was 0.76 +/- 0.3%. By day 3, it reached a peak of 4.1 +/- 1.1%, and then declined to its initial level. Following bromobenzene poisoning, hepatocyte and bile duct epithelia turn over in the same fashion. In both, labeling index and progenitor compartment size initially rise and return by the end of the first week to their initial level. We propose that bile duct epithelia and hepatocytes originate in one determined uncommitted stem cell that resides in the Herring duct. Bromobenzene-induced necrosis triggers proliferation of progenitors in both cell lineages, as well as in the stem cell itself.

Animals↗
PubMed1995

Normative medicine.

Normative medicine is a new approach to health and disease based on Canguilhem's philosophy: The normal and the pathological. In the past, disease was nearly synonymous with ill health. Advancing technology reveals more and more pre-clinical aberrations that are not fully fledged diseases, and cannot be regarded as ill health. Medicine lacks clear guidelines for dealing with them. While competent in specifying how to treat, it generally fails to decide correctly when to intervene in the evolving process. This is the main source of medical iatrogenesis. Normative medicine is more concerned with health itself and less with diseases. It provides criteria when to intervene in the disease process.

Epidemiologic Methods↗
PubMed1995

Streaming organism.

The cell kinetic characteristic of all epithelia is the same. All are analogs of the crypt-villus unit of the gastrointestinal mucosa. Each unit is nourished by at least one determined uncommitted stem cell (DS). When the DS divides, one of its progeny replaces the parent and remains a DS, while the other starts streaming outward. When entering a differentiation pathway it is called a committed stem cell (CS). Cells in the unit differentiate while streaming. Initially they continue multiplying and are called amplifying progenitors (P-cells), then they lose the capacity to synthesize DNA and become non-dividing (quiescent) end cells (Q-cells). All cells except the DS are transitional and short lived (in the crypt they live several days): only the DS is permanent. Since epithelial tissues are cell kinetic analogs of the crypt, it is assumed here that their neoplastic progression is analogous with the adenoma-carcinoma sequence of the crypt. Neoplasia starts when a normal cell is transformed into a neoplastic. If a transitional cell is hit by a carcinogen and transformed into a neoplastic, it soon will be washed out from the system. Only a transformed DS can maintain the neoplastic trait since it never leaves the crypt. Neoplasia is thus a pathology of the DS. There are two differentiation scales in the embryo: global and local. The first starts with the fertilized ovum that divides into stem cells that become more and more determined. Following gastrulation each determined stem cell generates its local progeny of transitional cells that make the tissue units. Determined stem cells are direct descendants of the fertilized ovum, while their transitional progenitors are direct descendants of determined stem cells.

Adenoma↗