Kokomo family care: automating the clinical practice.

A 14-physician family practice automated its prescription process, telephone messaging and laboratory test reporting to streamline its operations and contain costs.

Physiological significance of early deceleration time prolongation in asymptomatic elderly subjects.

BACKGROUND: Alterations in Doppler-derived diastolic filling patterns are common among elderly persons, but their physiological and prognostic significance remains uncertain, particularly in asymptomatic older persons without overt cardiac disease. This study was designed to determine whether early mitral inflow deceleration time (DT) prolongation is of physiological significance in asymptomatic elderly subjects. METHODS AND RESULTS: In 15 asymptomatic patients aged 60 to 93 years with no history of heart failure (HF) or edema, we performed two-dimensional and Doppler echocardiography and 60-minute head-out, isothermic water immersion to produce circulatory volume expansion. Plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured immediately before and after water immersion. Seven of 15 patients had a normal mitral early DT (160 to 240 milliseconds; group 1) and 8 of 15 patients had DT prolongation (> 240 milliseconds; group 2). Group 2 subjects had significantly smaller chamber sizes and increased relative wall thickness without increased left ventricular mass. Head-out water immersion produced greater increases in plasma ANP levels in group 2 subjects with longer DTs despite similar degrees of circulatory volume expansion in each group. In contrast, plasma BNP levels did not increase significantly with water immersion in either group. CONCLUSION: Early DT prolongation in asymptomatic elderly subjects is associated with increased relative wall thickness and enhanced ANP increments after central volume expansion. Such exaggerated responses suggest that, in the elderly, a prolonged DT has physiological significance and may represent a precursor to symptomatic diastolic HF, a condition known to be associated with advancing age.

Quality management in Irish health care.

This paper reports on the findings from a quantitative research study of quality management in the Irish health-care sector. The study findings suggest that quality management is what hospitals require to become more cost-effective and efficient. The research also shows that the culture of health-care institutions must change to one where employees experience pride in their work and where all are involved and committed to continuous quality improvement. It is recommended that a shift is required from the traditional management structures to a more participative approach. Furthermore, all managers whether from a clinical or an administration background must understand one another's role in the organisation. Finally, for quality to succeed in the health-care sector, strong committed leadership is required to overcome tensions in quality implementation.

Birth and fate of proliferative cells in the inner nuclear layer of the mature fish retina.

In teleost fish, unlike other vertebrates, the retina continues to grow throughout the animal's life both by stretching of the mature tissue and by the addition of new cells. Following larval development, new retinal cell birth is known to occur in a rim at the periphery of the mature retina and in the outer nuclear layer (ONL). We have now found that cell birth and proliferation also occurs in the inner nuclear layer (INL) of the mature fish retina. In rainbow trout (Onchoryncus mykiss), proliferative cells exist in the INL of fish of all ages, at least up to 2 years posthatching. The proliferative cells form clusters in the INL that align in radial columns, reaching from the inner to the outer plexiform layers. The density of proliferative cell clusters changes along the equatorial plane of the retina and is highest near both the nasal and temporal poles. Our data suggest that, after birth, the proliferative cells migrate away from the INL and into the ONL, with a half-time of about 3 days, and their cell bodies can be seen in the outer plexiform layer. Once they are in the ONL, the proliferative cells continue to divide and likely give rise to the precursor cells that differentiate into new rod photoreceptors.

Maximizing drug compliance in the elderly. Tips for staying on top of your patients' medication use.

The old joke goes, "I finally got it all together, but now I forget where I put it. "So it is for many older patients facing complicated disease management plans. They think they understand, but then the instructions blur or they forget if they took the medications or they become concerned that the drugs cost too much and decide to cut back. Taking care of themselves is suddenly just too complicated. Drs Ennis and Reichard look at the issues and present some strategies to improve compliance among the elderly.

Mutations and sequence variants in the testis-determining region of the Y chromosome in individuals with a 46,XY female phenotype.

The testis-determining gene SRY (sex determining region, Y) is located on the short arm of the Y chromosome and consists of a single exon, the central third of which is predicted to encode a conserved motif with DNA binding/bending properties. We describe the screening of 26 patients who presented with 46,XY partial or complete gonadal dysgenesis for mutations in both the SRY open reading frame (ORF) and in 3.8 kb of Y-specific flanking sequences. DNA samples were screened by using the fluorescence-assisted mismatch analysis (FAMA) method. In two patients, de novo mutations causing complete gonadal dysgenesis were detected in the SRY ORF. One was a nonsense mutation 5' to the HMG box, whereas the other was a missense substitution located at the C terminus of the conserved motif and identical to one previously detected in an unrelated patient. In addition, two Y-specific polymorphisms were found 5' to the SRY gene, and a sequence variant was identified 3' to the SRY polyadenylation site. No duplications of the DSS region in 20 of these patients were detected.

Localisation of a gene for central areolar choroidal dystrophy to chromosome 17p.

Central areolar choroidal dystrophy (CACD) is a rare inherited retinal disease which causes progressive profound loss of vision in patients during their 4th decade. We have identified a Northern Irish family with 19 affected individuals in three living generations. We have performed a total genome search and established linkage of CACD in this family to chromosome 17p (multipoint Zmax = 5.65 at D17S938). The genes for phosphatidylinositol transfer protein (PITPN), retinal guanylate cyclase (GUC2D), beta-arrestin 2 (ARRB2), pigment epithelium-derived factor (PEDF) and recoverin (RCV1) map to this region and are candidate genes for retinal disease. Analysis of the coding region of the PITPN gene failed to reveal any mutation in this family.

T-lymphocyte colony formation by lymphocytes from patients with aplastic anaemia.

T-lymphocyte colonies were cultured using lymphocytes from patients with aplastic anaemia and normal donors to assess their respective proliferative activities. Colony numbers from aplastic patient's cells were lower than from normal donors', though this was not significant. When lymphocytes from patients were co-cultured with normal lymphocytes, inhibition of T-colony formation was observed in 8 out of 12 experiments. As the degree of inhibition was greater than if patient cells grew no colonies, then, clearly, normal T-colony formation was inhibited. This ability of patients' lymphocytes to suppress lymphopoiesis might account for the low levels of patient T-colony formation, as well as low in vivo numbers of lymphocytes found in patients with aplastic anaemia. The role of patients' lymphocytes in causing marrow aplasia was investigated. Although the incorporation of patients' lymphocytes in normal granulocyte-macrophage (GM) colony-forming systems inhibited colony growth, in only 1 out of 8 patients was this inhibition significantly greater than that caused by the addition of normal lymphocytes to GM colony systems. Therefore, lymphocytes may not be the primary cause of aplastic anaemia, except for a few rare cases.

Successful remission induction with deoxycoformycin in elderly patients with T-helper prolymphocytic leukaemia.

Two elderly patients with prolymphocytic leukaemia (PLL) of T helper phenotype were treated with the adenosine deaminase inhibitor--deoxycoformycin--and achieved remission. The first patient has remained in an unmaintained remission for over a year. The second patient, treated with a regime which produced less side effects, subsequently relapsed in skin and lymph nodes and died. In view of the rarity of this condition a multi-centre assessment of the effectiveness of deoxycoformycin is indicated. T-lymphocyte colony formation in both cases was found to be reduced. Co-culture of the patients' lymphocytes with nonadherent mononuclear cells from normal individuals also showed inhibition of T-colony formation indicating that lack of nutrients or accessory cells was not responsible for low T-colony forming capacity.

The effects of various levels of intraocular pressure on the rabbit's outflow system.

The effects of various levels of intraocular pressure on the morphology of the rabbit outflow system were investigated. In a total of 20 rabbits, intraocular pressure was maintained at various levels between 0-50 mmHg in the experimental eye and at 20 mmHg in the control eye for 1 hr. Flow rates into the eyes were measured by following the movement of a miniscus through a calibrated capillary tube. Progressive increase in pressure lead to distension and enlargement of the ciliary cleft. The meshwork tissues stretched and distended, and the vessels of the angular aqueous plexus had pressure-sensitive giant vacuoles of their endothelium. These vessels were prone to closure at pressures of 30 mmHg and greater. Difficulties associated with quantitation of giant vacuoles in this species were discussed.

Lymphocytes from patients receiving lithium do not inhibit CFU-C growth.

Lymphocyte subset levels and function were examined in 12 patients on lithium therapy and in 11 healthy hospital personnel. Co-culture of allogeneic human bone marrow cells with monocyte-depleted lymphocyte preparations revealed that CFU-C formation was significantly reduced (mean 43% inhibition) in the presence of normal lymphocytes but not with the patients' lymphocytes (less than 5% inhibition). This did not reflect numerical changes in lymphocyte subsets, since these were similar for control and lithium subjects. T colony formation was significantly depressed in the patient group (P less than 0.05), whereas B colony numbers were similar in both groups (P greater than 0.1). The possible role of HLA-incompatibility affecting CFU-C growth was investigated in co-culture experiments, using lymphocytes from HLA-identical twins, one of whom was receiving lithium. In four separate co-culture experiments, the inhibitory effect was shown with lymphocytes from the non-lithium twin but was not demonstrated by the lithium subject. Addition of lithium in vitro to co-cultures of normal marrow and lymphocytes was found to negate the inhibitory phenomenon in a dose-related manner. It is postulated that granulocytosis induced by the administration of lithium may be a manifestation of changes in a lymphocytic control system.

Calcitonin gene-related polypeptide as a mediator of the neurogenic ocular injury response.

Calcitonin gene-related polypeptide (CGRP) has been localised immunochemically within the rat and guinea pig anterior uvea to nerve fibres of trigeminal origin. As with substance P (1-3) the level of CGRP in the iris-ciliary body is depleted after thermal damage to the Gasserian ganglion and elevated in chronically sympathectically denervated eyes. Unlike substance P, a potent pupillary constrictor (4,5), CGRP has no notable miotic action, but does, however, cause an elevation of the intraocular pressure (IOP) accompanied by disruption of the blood-aqueous barrier. It is proposed that the diverse actions of these two sensory neuropeptides conjointly mediate the antidromic ocular injury response.

An animal model of filtration surgery.

An animal model for glaucoma fistulising surgery is described. The model is designed to fail after a few weeks. It is suggested that the model may be used to investigate the effects of topical or systemic agents on the results of glaucoma surgery. The preliminary results of intraocular pressure and facility of outflow in the control group of rabbits are presented.

Changes in substance P- and neuropeptide Y-immunoreactive fibres in rat and guinea-pig irides following unilateral sympathectomy.

Substance P (SP)-immunoreactive fibres have been found in the rat and guinea-pig irides. They are distributed parallel to the pupillary margin in the sphincter muscle, and in an irregular plexus in the dilator muscle of both species. Neuropeptide Y (NPY)-immunoreactive fibres have also been demonstrated in the anterior uvea, displaying a pattern similar to that of the adrenergic nerves. One month after sympathectomy, there was an increase both in the density and possibly in the number of SP-immunoreactive fibres in the denervated irides of both rodent species. In the sympathectomized iris, there was a very notable decrease in the density of NPY-immunoreactive fibres indicating that the NPY peptide most likely coexists with the classical sympathetic neurotransmitter, noradrenaline, in the sympathetic nerve supply derived from the superior cervical ganglion. The disappearance of dopamine beta-hydroxylase (DBH) immunostaining fibres confirmed the success of the sympathetic denervation.

Circulating T-cell subpopulations in lithium-associated granulocytosis.

Granulocytosis is a common feature in patients undergoing lithium therapy. With increasing evidence that T lymphocytes play a role in the control of granulopoiesis, we have investigated the effect of lithium administration on circulating levels of T helper and T suppressor cells, as identified by monoclonal antibodies, to determine whether lithium-induced granulocytosis is mediated through changes in peripheral blood T cell subsets. Lithium carbonate was administered to 10 subjects over a 2 week period. Differential leucocyte counts and T, B, T helper and T suppressor lymphocyte enumerations were performed prior to administration of lithium (Day 1) and on 2 occasions (Day 7 and 14) during ingestion of the drug. Ten healthy control subjects were similarly investigated. Small, but significant elevation (p less than 0.05) in neutrophil counts at 7 and 14 days were observed in subjects taking lithium, serum lithium levels at these times were 0.56 +/- 0.27 and 0.68 +/- 0.17 mmol/l, respectively; lymphocyte and monocyte levels were unaffected. The percentages and absolute numbers of circulating T, B, T helper and T suppressor lymphocytes were not significantly altered (p greater than 0.05) during lithium administration and did not differ significantly (p greater than 0.05) from those recorded for the control group. We were thus unable to demonstrate that short-term lithium administration induced changes in the circulating levels of T helper (OKT4+) or T suppressor (OKT8+) cells.

Circulating human antibodies as a cause of falsely depressed ferritin values.

We have previously reported spuriously elevated values for serum thyrotropin (TSH) measured by immunoradiometric assay (IRMA). We tested those sera showing interference with the TSH assay in a ferritin IRMA which used 125I-rabbit antiferritin antibody and solid phase goat antiferritin antibody as reagents and spleen ferritin as standard. In this assay, we obtained falsely low ferritin values that were corrected by addition of 0.2% non-immune rabbit serum to the labelled antibody. Two other radioimmunoassays gave results with these sera that were not falsely lowered. The interference was shown to be due to human IgG reactive with rabbit serum, the specificity of the interfering antibody being similar in all affected sera. Human antibodies directed against immunoassay reagents may lead to spuriously increased or decreased immunoassay results depending on the specific reagents involved.