Death anxiety predicts fear of Cancer recurrence and progression in ovarian Cancer patients over and above other cognitive factors.

Death anxiety is understudied in people with cancer, especially in relation to fear of cancer recurrence (FCR) and fear of progression (FOP). The present study aimed to identify if death anxiety can predict FCR and FOP over and above other known theoretical predictors. One hundred and seventy-six participants with ovarian cancer were recruited for an online survey. We included theoretical variables, such as metacognitions, intrusive thoughts about cancer, perceived risk of recurrence or progression, and threat appraisal, in regression analyses to predict FCR or FOP. We investigated whether death anxiety added to the variance over and above these variables. Correlational analyses demonstrated that death anxiety is more strongly associated with FOP than FCR. The hierarchical regression including the theoretical variables described above predicted 62-66% of variance in FCR and FOP. In both models, death anxiety predicted a small but statistically significant unique variance in FCR and FOP. These findings draw attention to the importance of death anxiety in understanding FCR and FOP in people with a diagnosis of ovarian cancer. They also suggest that elements of exposure and existentialist therapies may be relevant in treating FCR and FOP.

Temperature dependence studies of adriamycin uptake and cytotoxicity.

In order to learn whether a direct relationship exists between cellular uptake and cytotoxicity of Adriamycin, we have compared the temperature dependencies of these two processes in L1210 cells. We find that the equilibrium concentration of drug taken inside the cells varies smoothly with temperature between 37 degrees C and 0 degree C. Even at 0 degree C, however, there is still measurable uptake of the drug into cells. The cytotoxicity index (cloning in soft agar), on the other hand, does not parallel the uptake temperature dependence. Cytotoxicity rapidly diminishes as the temperature of drug exposure is lowered; at all temperatures below about 20 degrees C, Adriamycin is not active. In contrast, other cytotoxic anticancer drugs like mitomycin C, bleomycin, and ARK 73-21 (a platinum analogue) retain cytotoxic potency at low temperatures. The inability of Adriamycin to kill cells at low temperature persists even at very high drug concentrations where substantial quantities of drug enter the cells. The low temperature impotence is not a result of inoperative enzymes which could metabolize Adriamycin to an alkylating species or electron donor to oxygen, since NADH and NADPH dependent reductase activities show linear Arrhenius behavior with no indication of low temperature inactivity. Using purified L1210 plasma membranes with bound Adriamycin as a fluorescence polarization probe, we find evidence of a phase change in the cell surface occurring at the same temperature as the loss of biological activity (approximately equal to 20 degrees C). We conclude that Adriamycin induced cytotoxicity is not dictated solely by uptake, in apparent contradiction with mechanisms requiring an intracellular target. Moreover, the loss of cytotoxicity below 20 degrees C appears to be linked to a structural change in the cell surface membrane, supporting a role other than transport for this membrane in transducing Adriamycin action.

Selective inhibition of proteolytic enzymes in an in vivo mouse model for experimental metastasis.

Peptide aldehyde transition state analogue inhibitors of serine and cysteine proteases have been used to selectively inhibit proteases for which prior evidence supports a role in tumor cell metastasis. These enzymes include cathepsin B, urokinase plasminogen activator (PA), and thrombin. The inhibition constants of the peptidyl aldehyde inhibitors show that they are highly selective for a particular targeted serine or cysteine protease. The inhibitors are introduced by i.p. injection or by miniosmotic pumps into syngeneic C57BL/6 mice also given injections of B16-F10 melanoma cells, and the number of metastatic foci in the lung was determined. While the injection protocol gave an initially high but changing in vivo concentration of inhibitor over time, the minipump implant gave a constant steady state concentration of inhibitor over 5-7 days. Minipump infusion of leupeptin (acetylleucylleucylargininal), a strong inhibitor of cathepsin B at a steady state plasma concentration 1000-fold greater than its Ki(cathepsin B), gave no significant decrease in lung colonization by the B16 tumor cells. Ep475, a stoichiometric irreversible peptide inhibitor of cathepsin B-like proteases, also did not significantly inhibit metastatic foci formation. Introduction of selective inhibitors of urokinase PA, tert-butyloxycarbonylglutamylglycyl-argininal and H-glutamylglycylargininal at concentrations near its Ki, produced no significant decrease in mouse lung colonization. The selective thrombin inhibitor D-phenylalanylprolylargininal infused to a steady state concentration 100-fold greater than its Ki dramatically increased B16 melanoma colonization of mouse lung. The results indicate that neither secreted cathepsin B-like nor urokinase PA have roles in B16 colonization of mouse lung, while thrombin may have a role in preventing metastasis. These experiments do not eliminate roles for a cathepsin B-like enzyme or urokinase PA in the initial steps of the metastatic process.

The One-Stop Aortic Surveillance Clinic.

BACKGROUND: The principle of interval ultrasound surveillance of small abdominal aortic aneurysms (AAA) is well established. The fundamental principle of surveillance is that repair of AAA is a serious undertaking and the risk of the operation outweighs the risk of rupture in aneurysms less than 5.5 cm. Surveillance is well established but requires multiple visits to both the surgical clinic and the ultrasound department. REPORT: This report presents a system whereby the vascular surgeon is trained in the process of aortic sonography with a view to one-stop clinic assessment. After training of the main investigators in aortic sonography, the surgeons performed scans on the aortas of 80 consecutive patients and compared the scan result with the subsequent formal scan. DISCUSSION: Surgical and radiographer scans correlate very closely. It is believed that the one-stop aortic surveillance model is safe, accurate, and improves both the patient journey and clinic throughput.

The partial agonist activity of antagonist-occupied steroid receptors is controlled by a novel hinge domain-binding coactivator L7/SPA and the corepressors N-CoR or SMRT.

Steroid receptor antagonists, such as the antiestrogen tamoxifen or the antiprogestin RU486, can have inappropriate agonist-like effects in tissues and tumors. To explain this paradox we postulated that coactivators are inadvertently brought to the promoters of DNA-bound, antagonist-occupied receptors. The human (h) progesterone receptor (PR) hinge-hormone binding domain (H-HBD) was used as bait in a two-hybrid screen of a HeLa cDNA library, in which the yeast cells were treated with RU486. We have isolated and characterized two interesting steroid receptor-interacting proteins that regulate transcription in opposite directions. The first is L7/SPA, a previously described 27-kDa protein containing a basic region leucine zipper domain, having no known nuclear function. When coexpressed with tamoxifen-occupied estrogen receptors (hER) or RU486-occupied hPR or glucocorticoid receptors (hGR), L7/SPA increases the partial agonist activity of the antagonists by 3- to 10-fold, but it has no effect on agonist-mediated transcription. The interaction of L7/SPA with hPR maps to the hinge region, and indeed, the hPR hinge region squelches L7/SPA-dependent induction of antagonist-mediated transcription. Interestingly, pure antagonists that lack partial agonist effects, such as the antiestrogen ICI164,384 or the antiprogestin ZK98299, cannot be up-regulated by L7/SPA. We also isolated, cloned, and sequenced the human homolog (hN-CoR) of the 270-kDa mouse (m) thyroid/retinoic acid receptor corepressor. Binding of hN-CoR maps to the hPR-HBD. mN-CoR, and a related human corepressor, SMRT, suppress RU486 or tamoxifen-mediated partial agonist activity by more than 90%. This suppression is completely squelched by overexpression of the hPR H-HBD. Additionally, both corepressors reverse the antagonist-dependent transcriptional up-regulation produced by L7/SPA. Our data suggest that the direction of transcription by antagonist-occupied steroid receptors can be controlled by the ratio of coactivators to corepressors recruited to the transcription complex by promoter-bound receptors. In normal tissues and in hormone-resistant breast cancers in which the agonist activity of mixed antagonists predominates, steroid receptors may be preferentially bound by coactivators. This suggests a strategy by which such partial agonist activity can be eliminated and by which candidate receptor ligands can be screened for this activity.

Nuclear receptor coactivators and corepressors.

The nuclear receptors belong to a superfamily of proteins, many of which are ligand-regulated, that bind to specific DNA sequences and control specific gene transcription. Recent data show that, in addition to contacting the basal transcription machinery directly, nuclear receptors inhibit or enhance transcription by recruiting an array of coactivator or corepressor proteins to the transcription complex. In this review we define the properties of these putative coregulatory factors; we describe the basal and coregulatory factors that are currently known to interact with nuclear receptors; we suggest various mechanisms by which coactivators and corepressors act; we discuss issues that are raised by the presence of multiple, perhaps competing, coregulatory factors; and we speculate how these additional regulatory layers may explain the heterogeneity of hormone responses that are observed in normal and malignant tissues.

Microcirculation in the foot is augmented by neuromuscular stimulation via the common peroneal nerve in different lower limb postures: a potential treatment for leg ulcers.

OBJECTIVES: To examine the effects of the geko™ device (a portable electical nerve stimulator) on microcirculatory flow on the dorsum of the foot, and whether this is influenced by lower limb postures and application of a plaster cast. STUDY DESIGN: Cross-sectional, healthy cohort, open label, physiological response study. METHODS: In 10 healthy volunteers, aged 19 to 24 years, Laser Doppler Fluxmetry measurements were made on the dorsum of the foot in four postures: standing (weight bearing and non-weight bearing) and supine lying (with the lower limb horizontal and then elevated). Measurements of flux were made both at rest and during stimulation with the geko™ device applied over the common peroneal nerve, at 1Hz for 5 minutes in each posture. Repeat measurement were made after the application of a below knee plaster cast. Measures of flux were compared to basal levels assumed to be in supine with limb horizontal, with no cast and an inactive Geko device. RESULTS: The geko™ device was effective in increasing microcirculation on the dorsum of the foot in all four postures (Mean difference =141%, 95% CI 70%-212%, p=0.001). This effect was more pronounced than that of using a plaster alone (Mean increase in Flux of 73%, 95% CI 22%-125%, p=0.01) or variances due to the hydrostatic effects of different postures (Mean difference 17-27.6%, p>0.05). There was a 2 to 3 fold increase in flux when stimulation was delivered in combination with the plaster cast. CONCLUSIONS: Stimulation using the geko™ device augments microcirculation in the foot. The response is greater in lying and non-weight bearing than weight bearing standing but the most striking effect is when stimulation is combined with a plaster cast. The geko™ offers a potential means of promoting conditions favourable for wound healing, where treatment using compression may be contraindicated, such as arterial/mixed aetiology ulcers.

Microcirculation in the foot is augmented by neuromuscular stimulation via the common peroneal nerve in different lower limb postures: a potential treatment for leg ulcers.

AIM: Aim of the study was to examine the effects of the geko™ device (a portable electical nerve stimulator) on microcirculatory flow on the dorsum of the foot, and whether this is influenced by lower limb postures and application of a plaster cast. METHODS: This was a cross-sectional, healthy cohort, open label, physiological response study. In 10 healthy volunteers, aged 19 to 24 years, laser Doppler fluxmetry measurements were made on the dorsum of the foot in four postures: standing (weight bearing and non-weight bearing) and supine lying (with the lower limb horizontal and then elevated). Measurements of flux were made both at rest and during stimulation with the geko™ device applied over the common peroneal nerve, at 1 Hz for 5 minutes in each posture. Repeat measurement were made after the application of a below knee plaster cast. Measures of flux were compared to basal levels assumed to be in supine with limb horizontal, with no cast and an inactive geko™ device. RESULTS: The geko™ device was effective in increasing microcirculation on the dorsum of the foot in all four postures (mean difference =141%, 95% CI 70%-212%, P=0.001). This effect was more pronounced than that of using a plaster alone (Mean increase in flux of 73%, 95% CI 22%-125%, P=0.01) or variances due to the hydrostatic effects of different postures (mean difference 17-27.6%, P>0.05). There was a 2 to 3 fold increase in flux when stimulation was delivered in combination with the plaster cast. CONCLUSION: Stimulation using the geko™ device augments microcirculation in the foot. The response is greater in lying and non-weight bearing than weight bearing standing but the most striking effect is when stimulation is combined with a plaster cast. The geko™ offers a potential means of promoting conditions favourable for wound healing, where treatment using compression may be contraindicated, such as arterial/mixed aetiology ulcers.

The first extracellular domain of corticotropin releasing factor-R1 contains major binding determinants for urocortin and astressin.

The CRF receptors are members of a 7-transmembrane receptor family that includes GH-releasing hormone (GRF), calcitonin, vasoactive intestinal peptide (VIP), secretin, and PTH receptors. To determine the structural features of the CRF receptor that may influence ligand recognition, a series of mutant receptors was analyzed for binding to astressin, a CRF antagonist, and to urocortin, a CRF agonist. Mutant receptors included chimeras between the CRF-R1 and GRF-R or Activin IIB-R, a single membrane spanning receptor serine/threonine kinase. Binding to the mutant receptors was assessed using 125I-[DTyr1] astressin (Ast*) and 125I-[Tyr0]-rat urocortin (Ucn*). There was no binding to a chimeric receptor in which the first extracellular domain (E1c) (i.e. the N-terminal region) of the CRF-R1 was replaced by that of the GRF-R. The complementary chimera in which E1 domain of the GRF-R was replaced by that of the CRF-R1 bound astressin and urocortin with Ki values approximately 10 nM, compared with inhibitory binding dissociation constant (Ki) values of approximately 2-4 nM for the wild-type CRF-R1. The chimera in which E1 of the activin IIB receptor was replaced by E1 of the CRF-R1 bound astressin with a Ki approximately 4 nM. A chimera in which both the first and fourth extracellular domains of the CRF-R1 replaced the corresponding domains of the GRF-R bound astressin with Ki approximately 4 nM and urocortin with a Ki approximately 2 nM. A chimera in which all four extracellular domains of the CRF receptor replaced those of the GRF-R bound astressin and urocortin with Ki values approximately 4 nM and approximately 1 nM, respectively. In conclusion, the major determinants for high affinity binding of CRF agonists and antagonists to CRF-R1 are found in the first extracellular domain of the receptor.

Use of recombinant vectors derived from herpes simplex virus 1 mutant tsK for short-term expression of transgenes encoding cytoplasmic and membrane anchored proteins in postmitotic polarized cortical neurons and glial cells in vitro.

We constructed three recombinant vectors derived from the herpes simplex virus type 1 mutant tsK, each of which contained a different transgene under the control of the herpes simplex virus type 1 immediate early 3 promoter inserted into the thymidine kinase locus: the prokaryotic enzymes beta-galactosidase and chloramphenicol acetyl transferase, and a fusion gene consisting of human tissue inhibitor of metalloproteinases linked to the last exon of Thy-1, which encodes for a glycosyl-phosphatidyl-inositol membrane anchor. Infection of postmitotic neocortical and hippocampal neurons in low-density primary cultures with these vectors, achieved reliable expression of all three foreign gene products in various neocortical cell types, e.g. pyramidal neurons, non-pyramidal neurons, and glial cells. The percentage of neurons expressing transgenes ranged from 1 to 46% depending on the multiplicity of infection (highest assayed = 5); the percentage of glial cells expressing transgenes ranged from 0.5 to 98% (highest multiplicity assayed = 3.4). Expression of transgenes could be detected for up to three days in approximately 20% of neurons infected at a multiplicity of infection of 1. Infection of neurons with tk K-derived recombinant vectors inhibited their protein synthesis by 40-50% at a multiplicity of infection of 10, but no effect was observed at a multiplicity of infection of 1. Infection of glial cells with the same vectors at a multiplicity of infection of 1 inhibited protein synthesis by more than 90%. Analysis of neuronal viability at different times post-infection indicated that more than 98% of neurons expressing transgenes 48 h post-infection were viable. Thus, low-density neuronal cultures can be used to assess the efficiency of herpes simplex virus type 1-derived gene transfer vectors and transgene expression in developing cortical postmitotic cells, before and after they establish polarity. In addition, we show that two cytoplasmic enzymes, beta-galactosidase and chloramphenicol acetyl transferase, are able to diffuse freely in the cytoplasm reaching even growth cones in young neurons, while the chimeric protein tissue inhibitor of metalloproteinases/Thy-1 is correctly targeted to the plasma membrane via a glycosyl-phosphatidylinositol anchor. This model system should be useful for investigation of cellular and molecular aspects of the development and establishment of neuronal polarity, as well as for analysis of signals involved in protein targeting in postmitotic neurons.

Adrenergic differentiation potential in PC12 cells: influence of sodium butyrate and dexamethasone.

The ability of sodium butyrate and dexamethasone to promote adrenergic differentiation in PC12 cells was examined using the gene encoding the epinephrine biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT), as a marker. Sodium butyrate and dexamethasone independently stimulated expression of PNMT mRNA in PC12 cells, and the combined action of these drugs led to synergistic activation of the PNMT gene. Despite the induction of the PNMT gene, epinephrine is not produced in these cells, in part due to the absence of a corresponding induction in PNMT enzymatic activity. Another contributing factor appears to be a reduction in the precursor catecholamines, norepinephrine and dopamine, in the presence of sodium butyrate. Thus, while sodium butyrate and dexamethasone can induce PNMT gene expression, treatment of PC12 cells with these drugs appears insufficient for full acquisition of the adrenergic phenotype.

Simultaneous detection of amplicon and HSV-1 helper encoded proteins reveals that neurons and astrocytoma cells do express amplicon-borne transgenes in the absence of synthesis of virus immediate early proteins.

HSV-1 amplicon vectors were used to express either a cytoplasmic (beta-galactosidase) or a membrane targeted protein (TIMP-Thy1) in primary neuronal cultures, and a human astrocytoma cell line. Whereas some cells became infected by vector particles alone others were simultaneously infected by both vector and helper particles. Our results show that IEHCMV and HSV-1 IE3 promoters are able to direct transgene expression in these cells in the absence of synthesis of helper virus transacting proteins, and stress the need of monitoring expression from both partners of an amplicon population, in order to differentiate transgene expression in cells singly infected with amplicon particles, from those infected by both amplicon and helper particles.

Characteristics of family practitioners with large geriatric practices.

Little has been reported on the characteristics of physicians presently serving the health needs of the elderly. In this report, generated from a survey of Florida family practitioners, physicians and with large geriatric practices are compared to physicians with practices composed primarily of younger patients. Family physicians with large geriatric practices are older, and treat more chronic disease than do their peers. However, they consult the same professional journals and texts in caring for their patients, refer patients to specialists at the same rate, and have the same office facilities as do their colleagues who treat chiefly younger patients. The family physician with a large geriatric case load is less likely to have a predominantly outpatient practice and more likely to be involved with hospitalized patients. Data from the census and health manpower studies suggest that family physicians will care for substantial number of elderly patients in the future. Continuing education which addresses issues in geriatrics may help to attain optimal health care for the elderly.

Thoughts on tamoxifen resistant breast cancer. Are coregulators the answer or just a red herring?

The antiestrogen tamoxifen is an effective treatment for estrogen receptor positive breast cancers, slowing tumor growth and preventing disease recurrence, with relatively few side effects. However, many patients who initially respond to treatment, later become resistant to treatment. Tamoxifen has both agonist and antagonist activities, which are manifested in a tissue-specific pattern. Development of tamoxifen resistance can be characterized by an increase in the partial agonist properties of the antiestrogen in the breast, resulting in loss of growth inhibition and even inappropriate tumor stimulation. Nuclear receptor function is modulated by transcriptional coregulators, which either enhance or repress receptor activity. Using a mixed antagonist-biased two-hybrid screening strategy, we identified two such proteins: the human homolog of the nuclear receptor corepressor, N-CoR, and a novel coactivator, L7/SPA (Switch Protein for Antagonists). In transcriptional studies N-CoR suppressed the agonist properties of tamoxifen and RU486, while L7/SPA increased agonist effects. We speculated that the relative level of these coactivators and corepressors might determine the balance of agonist and antagonist properties of mixed antagonists such as tamoxifen. Using quantitative RT-PCR we therefore measured the levels of transcripts encoding these coregulators, as well as the corepressor SMRT, and the coactivator SRC-1, in a small cohort of tamoxifen resistant and sensitive breast tumors. The results suggest that tumor sensitivity to mixed antagonists may be governed by a complex set of transcription factors, which we are only now beginning to understand.

Herpes simplex virus 1 (HSV-1) helper co-infection affects the distribution of an amplicon encoded protein in glia.

HSV-1 derived amplicons expressing cytoplasmic beta-galactosidase (pA-SF1), or plasma membrane targeted TIMP-Thy1 (pA-TT1), were used to transduce glial cells in vitro. By monitoring the expression of reporter genes from both amplicons and helper virus, we determined that many cells were infected by both particles. In glial cells infected only by pA-SF1 beta-galactosidase immunoreactivity was restricted to the cytoplasm; co-infection with helper HSV-1 (wild type), resulted in additional nuclear beta-galactosidase immunoreactivity. Co-infection of cells with amplicon pA-TT1 and helper virus did not affect the plasma membrane localization of TIMP/Thy1. Thus, co-infection with wild type helper virus altered the localization of an amplicon encoded cytoplasmic, but not plasma membrane protein.

Accuracy and precision of the CellForm-Human automated sperm morphometry instrument.

OBJECTIVE: To evaluate the accuracy and precision of the CellForm-Human (CFH) automated sperm morphometry instrument (Motion Analysis Corp., Santa Rosa, CA). SETTING: Clinical and research andrology and in vitro fertilization laboratories. PATIENTS: Individuals undergoing semen evaluation and infertility work-up. RESULTS: Coefficients of variation for repeated measures of the same sperm were 1%. Coefficients of variation of normal sperm measurements were 7.4% to 12.8%, depending on the measure. Of the objects recognized as sperm by the instrument, 6.8% were debris; hence, the sperm recognition algorithms need improvement. Mean values for all CFH measures of normal sperm from specimens clinically classified as having predominantly normal, tapered, or amorphous sperm were not different; hence, the morphometry of normal sperm from normal specimens was similar to normal sperm from specimens with two different abnormalities. The instrument classified sperm as abnormal if their length or width fell outside a critical range of values recommended by the World Health Organization. Using this method, manual and CFH classification agreed unambiguously 60% of the time. When disagreement occurred, length or width marginally exceeded the range by no more than 0.1 microns. In these cases, the technician classified sperm as normal 25% of the time and classified them as abnormal 6% of the time. Because this disagreement between methods is well below the resolution of manual methods, the overall accuracy of CFH was 91% for cell type classification. CONCLUSION: At its present stage of development, the CFH instrument exceeds the accuracy and precision of most manual approaches. With improvements in sperm recognition and type classification algorithms, it could significantly improve the reliability of morphology assays in clinical and research laboratories.

Nuclear receptor conformation, coregulators, and tamoxifen-resistant breast cancer.

The development of tamoxifen resistance and consequent disease progression are common occurrences in breast cancers, often despite the continuing expression of estrogen receptors (ER). Tamoxifen is a mixed antagonist, having both agonist and antagonist properties. We have suggested that the development of tamoxifen resistance is associated with an increase in its agonist-like properties, resulting in loss of antagonist effects or even inappropriate tumor stimulation. Nuclear receptor function is influenced by a family of transcriptional coregulators, that either enhance or suppress transcriptional activity. Using a mixed antagonist-biased two-hybrid screening strategy, we identified two such proteins: the human homolog of the nuclear receptor corepressor, N-CoR, and a novel coactivator, L7/SPA (Switch Protein for Antagonists). In transcriptional studies, N-CoR suppressed the agonist properties of tamoxifen and RU486, and L7/SPA increased agonist effects. We speculated that the relative levels of these coactivators and corepressors may determine the balance of agonist and antagonist properties of mixed antagonists, such as tamoxifen. Using quantitative RT-PCR, we, therefore, measured the levels of transcripts encoding these coregulators, as well as the corepressor SMRT, and the coactivator SRC-1, in a small cohort of tamoxifen-resistant and sensitive breast tumors. The results suggest that tumor sensitivity to mixed antagonists may be governed by a complex set of transcription factors, which we are only now beginning to understand.

Evaluation of biodegradable rifampicin-bearing microsphere formulations using a stability-indicating high-performance liquid chromatographic assay.

The validation of a rapid and selective stability-indicating high-performance liquid chromatographic procedure for the determination of rifampicin (RIF) and its decomposition products in aqueous solution is described. Direct injection and column switching HPLC procedures have been compared and, owing to the increased sensitivity and precision, the latter has been applied to the study of RIF stability in the presence of isoascorbic acid at pH 7.4. The time-dependent hydrolytic decomposition of RIF to 3-formyl rifamycin SV (RSV) was found to be biexponential. Log concentration versus time plots of RIF and RSV decomposition were found to be parallel, indicating a pseudo equilibrium decomposition process. This feature allowed corrections for the amounts lost to secondary reactions to be calculated when the assay was applied to the determination of release characteristics of RIF from biodegradable poly-d, l-lactide-co-glycolide microspheres.

Consortium building among local health departments in northwest Illinois.

The 1947 report by Haven Emerson envisioned the widespread delivery of local public health services through organizational patterns that substituted multi-county or regional agencies for locally controlled departments. The 1971 study by Vlado Getting supported the Emerson report and suggested alternative methods to provide public health services via multi-county area health service agencies for rural areas of Illinois. The number of local agencies in the State has doubled since the mid-1960s, yet a majority of rural counties have maintained a single-county health agency rather than forming multi-county arrangements. In effect, potential economies of scale have been forfeited. In northwest Illinois, however, eight local health departments, covering both rural and urban areas, have formed a multi-county consortium to identify and meet several overlapping program needs. This Region I consortium, with a population base of 590,000, was created as a result of the 1981 Omnibus Budget Reduction Act. Through the block grants created by the act, funds became available for preventive health and health promotion activities in fiscal year 1982. Once in place, the consortium provided a cost effective means to manage the Women, Infants, and Children Supplemental Feeding Program (WIC) and some elements of family planning programs in Region I. The consortium approach offers numerous opportunities for future growth and regionalization of services.

Histochemical changes in intestinal atresia and its implications on surgical management: a preliminary report.

Histochemical studies of the intestine were performed on five neonates, three with intestinal atresia and two as normal controls. In this preliminary report, changes secondary to ischemia and obstruction were defined. It was shown that the ischemic changes were limited in extent both proximally and distally, and the obstructive changes were reversible. A conservative approach to resection in the management of intestinal atresia is suggested. Limited resection of the dilated proximal bowel together with the use of total parenteral nutrition will allow for a safe waiting period for the pathological changes to reverse themselves and effective peristalsis to return.