Social work and general practice: A report of a three-year attachment

Much has been written about social worker/general-practitioner collaboration, particularly about conflict of roles, differing functions, avenues of accountability, and problems of distributing scarce resources.

We suggest that if the two professions are to work more comfortably together, then it is imperative that both also share the despair, hopelessness, anxiety, and anger that are the occupational hazards of each. We suggest ways in which doctors and social workers can look at the pain their patients are suffering to the benefit of the patient and their own working relationship.

     

Host susceptibility to the attaching and effacing bacterial pathogen Citrobacter rodentium

Many studies have shown that genetic susceptibility plays a key role in determining whether bacterial pathogens successfully infect and cause disease in potential hosts. Surprisingly, whether host genetics influence the pathogenesis of attaching and effacing (A/E) bacteria such as enteropathogenic and enterohemorrhagic Escherichia coli has not been examined. To address this issue, we infected various mouse strains with Citrobacter rodentium, a member of the A/E pathogen family. Of the strains tested, the lipopolysaccharide (LPS) nonresponder C3H/HeJ mouse strain experienced more rapid and extensive bacterial colonization than did other strains. Moreover, the high bacterial load in these mice was associated with accelerated crypt hyperplasia, mucosal ulceration, and bleeding, together with very high mortality rates. Interestingly, the basis for the increased susceptibility was not due to LPS hyporesponsiveness, as the genetically related but LPS-responsive C3H/HeOuJ and C3H/HeN mouse strains were also susceptible to infection. Analysis of the intestinal pathology in these susceptible strains revealed significant crypt epithelial cell apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end label staining) as well as bacterial translocation to the mesenteric lymph nodes. Further studies with infection of SCID (T- and B-lymphocyte-deficient) C3H/HeJ mice demonstrated that loss of lymphocytes had no effect on bacterial numbers but did reduce crypt cell apoptosis and delayed mortality. These studies thus identify the adaptive immune system, crypt cell apoptosis, and bacterial translocation but not LPS responsiveness as contributing to the tissue pathology and mortality seen during C. rodentium infection of highly susceptible mouse strains. Determining the basis for these strains' susceptibility to intestinal colonization by an A/E pathogen will be the focus of future studies.     

Identification of 6 new mutations in the iduronate sulfatase gene. Mutation in brief no. 233. Online

Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. We sequenced genomic DNA and RT-PCR products in the iduronate sulfatase (IDS) gene in 6 unrelated patients with Hunter syndrome to assess genotype/phenotype relationships and offer carrier testing where required. Six novel mutations were identified: four missense mutations, one four-base pair deletion (596-599delAACA) and a cryptic splice site mutation. Three of the missense mutations were significant amino acid substitutions (S143F, S491F, E341K) of which the latter two involve amino acids conserved amongst sulfatase enzymes. The patients identified with these mutations all had a severe clinical phenotype. One missense mutation with a minimal amino acid substitution (H342Y), in a non-conserved region of the gene, was associated with a mild clinical phenotype. We identified a novel cryptic splice site (IVS5+934G>A) with some normal (wild type) mRNA processing. We predict that the normal mRNA product confered some residual functional enzyme, resulting in a mild phenotype associated with the absence of overt central nervous system disease.     

Accessibility, clinical effectiveness, and practice costs of providing a telephone option for routine asthma reviews: phase IV controlled implementation study.

BACKGROUND: Attendance for routine asthma reviews is poor. A recent randomised controlled trial found that telephone consultations can cost-effectively and safely enhance asthma review rates; however, concerns have been expressed about the generalisability and implementation of the trial's findings. AIM: To evaluate the effectiveness of a telephone option as part of a routine structured asthma review service. DESIGN OF STUDY: Phase IV controlled before-and-after implementation study. SETTING: A large UK general practice. METHOD: Using existing administrative groups, all patients with active asthma (n = 1809) received one of three asthma review services: structured recall with a telephone-option for reviews versus structured recall with face-to-face-only reviews, or usual-care (to assess secular trends). Main outcome measures were: proportion of patients with active asthma reviewed within the previous 15 months (Quality and Outcomes Framework target), mode of review, enablement, morbidity, and costs to the practice. RESULTS: A routine asthma review was provided for 397/598 (66.4%) patients in the telephone-option group compared with 352/654 (53.8%) in the face-to-face-only review group: risk difference 12.6% (95% confidence interval [CI] = 7.2 to 17.9, P<0.001). The usual-care group achieved a review rate of 282/557 (50.6%). Morbidity was equivalent in the three groups; however, enablement (P = 0.03) and confidence (P = 0.007) in asthma management were greater in the telephone-option versus face-to-face-only group. The cost per review achieved by providing the telephone-option service was lower than the face-to-face-only service (10.03 pounds versus 12.74 pounds, mean difference 2.71 pounds; 95% CI = 1.92 to 3.50, P<0.001); usual-care costs were 11.85 pounds per review achieved. CONCLUSION: Routinely offering telephone reviews cost-effectively increased asthma review rates, enhancing patient enablement and confidence with management, with no detriment to asthma morbidity. Practices should consider a telephone option for their asthma review service.     

Preferential retention of human chromosome 14 in mouse × human B cell hybrids

Loss of human chromosomes from mouse × human hybridomas is not random. Human chromosomes 14, 5 and 22 are preferentially retained, while chromosomes 2 and 1 are preferentially lost. Interestingly, human chromosome 14, which carries the genes for human immunoglobulin heavy chains, appears to be retained by almost all the hybrid clones and subclones.     

Single-column thalamocortical network model exhibiting gamma oscillations, sleep spindles, and epileptogenic bursts

To better understand population phenomena in thalamocortical neuronal ensembles, we have constructed a preliminary network model with 3,560 multicompartment neurons (containing soma, branching dendrites, and a portion of axon). Types of neurons included superficial pyramids (with regular spiking [RS] and fast rhythmic bursting [FRB] firing behaviors); RS spiny stellates; fast spiking (FS) interneurons, with basket-type and axoaxonic types of connectivity, and located in superficial and deep cortical layers; low threshold spiking (LTS) interneurons, which contacted principal cell dendrites; deep pyramids, which could have RS or intrinsic bursting (IB) firing behaviors, and endowed either with nontufted apical dendrites or with long tufted apical dendrites; thalamocortical relay (TCR) cells; and nucleus reticularis (nRT) cells. To the extent possible, both electrophysiology and synaptic connectivity were based on published data, although many arbitrary choices were necessary. In addition to synaptic connectivity (by AMPA/kainate, NMDA, and GABA(A) receptors), we also included electrical coupling between dendrites of interneurons, nRT cells, and TCR cells, and--in various combinations--electrical coupling between the proximal axons of certain cortical principal neurons. Our network model replicates several observed population phenomena, including 1) persistent gamma oscillations; 2) thalamocortical sleep spindles; 3) series of synchronized population bursts, resembling electrographic seizures; 4) isolated double population bursts with superimposed very fast oscillations (>100 Hz, "VFO"); 5) spike-wave, polyspike-wave, and fast runs (about 10 Hz). We show that epileptiform bursts, including double and multiple bursts, containing VFO occur in rat auditory cortex in vitro, in the presence of kainate, when both GABA(A) and GABA(B) receptors are blocked. Electrical coupling between axons appears necessary (as reported previously) for persistent gamma and additionally plays a role in the detailed shaping of epileptogenic events. The degree of recurrent synaptic excitation between spiny stellate cells, and their tendency to fire throughout multiple bursts, also appears critical in shaping epileptogenic events.     

Optic flow signals in extrastriate area MST: comparison of perceptual and neuronal sensitivity

The medial superior temporal area of extrastriate cortex (MST) contains signals selective for nonuniform patterns of motion often termed "optic flow." The presence of such tuning, however, does not necessarily imply involvement in perception. To quantify the relationship between these selective neuronal signals and the perception of optic flow, we designed a discrimination task that allowed us to simultaneously record neuronal and behavioral sensitivities to near-threshold optic flow stimuli tailored to MST cells' preferences. In this two-alternative forced-choice task, we controlled the salience of globally opposite patterns (e.g., expansion and contraction) by varying the coherence of the motion. Using these stimuli, we could both relate the sensitivity of neuronal signals in MST to the animal's behavioral sensitivity and also measure trial-by-trial correlation between neuronal signals and behavioral choices. Neurons in MST showed a wide range of sensitivities to these complex motion stimuli. Many neurons had sensitivities equal or superior to the monkey's threshold. On the other hand, trial-by-trial correlation between neuronal discharge and choice ("choice probability") was weak or nonexistent in our data. Together, these results lead us to conclude that MST contains sufficient information for threshold judgments of optic flow; however, the role of MST activity in optic flow discriminations may be less direct than in other visual motion tasks previously described by other laboratories.     

Identification and isolation of a common tumor-associated molecule using monoclonal antibody

A monoclonal antibody, 16B-13, derived from the immunization of BALB/c mice with a lung tumor line, immunoprecipitates a common tumor-associated molecule with an apparent mol. wt of 37,000 from lactoperoxidase-ionated lung carcinoma, colon carcinoma, gastric carcinoma, brest carcinoma, melanoma and lymphona cells, but not from normal fibroblasts. Analysis by two-dimensional gel electrophoresis of the cell surface-labeled 16B-13 antigen from a colorectal and a melanoma cell line reveals four components with similar mol. wts but with different isoelectric points. The antigen purified froma a colorectal carcinoma cell line by immunoaffinity chromatography was shown to be a 37,000 mol. wt polypeptide similar to that obtained by the lactoperoxidase-labeling procedure. However, the purified antigen from the melanoma cell line shows the presence of a 65,000 mol. wt polypeptide and the loss of the 37,000 mol. wt component as detected by Comassie blue staining and immunoprecipitation.     

Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.