From diagnosis to social diagnosis

In the past two decades, research on the sociology of diagnosis has attained considerable influence within medical sociology. Analyzing the process and factors that contribute to making a diagnosis amidst uncertainty and contestation, as well as the diagnostic encounter itself, are topics rich for sociological investigation. This paper provides a reformulation of the sociology of diagnosis by proposing the concept of 'social diagnosis' which helps us recognize the interplay between larger social structures and individual or community illness manifestations. By outlining a conceptual frame, exploring how social scientists, medical professionals and laypeople contribute to social diagnosis, and providing a case study of how the North American Mohawk Akwesasne reservation dealt with rising obesity prevalence to further illustrate the social diagnosis idea, we embark on developing a cohesive and updated framework for a sociology of diagnosis. This approach is useful not just for sociological research, but has direct implications for the fields of medicine and public health. Approaching diagnosis from this integrated perspective potentially provides a broader context for practitioners and researchers to understand extra-medical factors, which in turn has consequences for patient care and health outcomes.     

The effect of interleukin-6 on pituitary hormone release in vivo and in vitro.

Intravenously administered interleukin-6 (IL-6), a monokine produced by activated monocytes and folliculostellate cells of the pituitary gland, has been recently reported to elevate plasma ACTH level and to stimulate PRL, GH and LH release from cultured pituitary cells. To determine the site(s) of action of IL-6 in the control of pituitary hormone release, we injected human recombinant IL-6 into the third brain ventricle (3V) of freely moving, conscious male rats. Both 0.05 and 0.25 pmol doses of IL-6 were ineffective to change plasma ACTH in comparison to the values in controls. The maximal IL-6 dose tested of 1.25 pmol increased plasma ACTH within 15 min and the response lasted over 180 min. Plasma TSH levels were significantly lowered by a dose of 0.25 pmol IL-6, but neither the lower dose of 0.05 pmol nor the higher dose of 1.25 pmol altered plasma TSH levels throughout the 180 min of the experiment. Plasma PRL and GH levels were not changed by any IL-6 dose tested. In ovariectomized rats plasma LH and FSH levels were also unaltered by IL-6. The effects of IL-6 on plasma ACTH and TSH were only partially paralleled by increased rectal temperature which suggests that hypothalamic temperature regulating centers were independent of these actions. To evaluate a possible direct effect on the pituitary, IL-6 was incubated in vitro with hemipituitaries under an atmosphere of 95% O2/5% CO2. After 1 h of incubation IL-6 failed to cause any change in the secretion of pituitary hormones throughout a concentration range of 10(-15)-10(-9) M.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identifying Profiles of Support for Legal Abortion Services in Zambia: A Latent Class Analysis

Relative to neighboring countries, Zambia has among the most progressive abortion policies, but numerous sociopolitical constraints inhibit knowledge of pregnancy termination rights and access to safe abortion services. Multistage cluster sampling was used to randomly select 1,486 women aged 15–44 years from households in three provinces. We used latent class analysis (LCA) to partition women into discrete groups based on patterns of endorsed support for legalized abortion on six socioeconomic and health conditions. Predictors of probabilistic membership in latent profiles of support for legal abortion services were identified through mixture modeling. A three-class solution of support patterns for legal abortion services emerged from LCA: (1) legal abortion opponents (∼58 percent) opposed legal abortion across scenarios; (2) legal abortion advocates (∼23 percent) universally endorsed legal protections for abortion care; and (3) conditional supporters of legal abortion (∼19 percent) only supported legal abortion in circumstances where the pregnancy threatened the fetus or mother. Advocates and Conditional supporters reported higher exposure to family planning messages compared to opponents. Relative to opponents, advocates were more educated, and Conditional supporters were wealthier. Findings reveal that attitudes towards abortion in Zambia are not monolithic, but women with access to financial/social assets exhibited more receptive attitudes towards legal abortion.     

Normal reference intervals and ranges of side-to-side and day-to-day variability of ocular blood flow Doppler parameters

The study presents normal reference intervals and ranges of "normal" side-to-side and day-to-day variability of ocular blood flow Doppler parameters. Peak-systolic (PSV), end-diastolic velocity (EDV) and impedance indices in the ophthalmic artery (OA), the central retinal artery (CRA) and the short posterior ciliary artery (SPCA) of both orbits were determined with color-coded duplex sonography in 140 healthy volunteers (range 18 to 83 y; 68 men and 72 women). Decreases in flow velocities and concomitant increases in impedance indices were found in all arteries with advancing age. The PSV and the EDV values for the OA, the CRA and the SPCA in the age group less than 40 yr-old were 40.6 +/- 8.9 and 11.2 +/- 3.7, 9.9 +/- 1.8 and 3.7 +/- 0.9, 13.8 +/- 2.6 and 5.7 +/- 1.5 cm/s (mean +/- SD), respectively. In the 40 to 60 yr-old age group, the values were 35 +/- 7.9 and 10.7 +/- 4.3, 9.7 +/- 2 and 3.5 +/- 0.8, 13.5 +/- 2.9 and 5.3 +/- 1.5 cm/s. In the age group over 60 yr-old, the values were 34 +/- 8 and 8.4 +/- 3.3, 9.3 +/- 2 and 3 +/- 0.9, 12.8 +/- 2.4 and 4.3 +/- 1.2 cm/s. In the youngest age group, the EDV in the CRA and the SPCA was higher in women, while in the OA the PSV and the EDV were higher in men. Ranges of side-to-side variability in the OA, the CRA and the SPCA, determined with repeatability coefficient for the PSV and the EDV, were 24, 5.4, 7.5 cm/s and 11, 2.5, 4.2 cm/s, respectively, whereas the values for day-to-day variability were 16.8, 4.3, 6.7 cm/s and 5.6, 1.7 and 3.9 cm/s. Ocular blood flow Doppler parameters range widely and are significantly age and sex dependent. Ranges of "normal" side-to-side and day-to-day variability of the parameters can help to determine abnormal flow pattern.     

The effect of nerve growth factor on DNA synthesis, cyclic AMP and cyclic GMP accumulation by mouse spleen lymphocytes.

Nerve growth factor (NGF), a trophic neuropeptide, is known to stimulate development, and to be important in the maintenance and survival of sympathetic and sensory neurons. Considering the presence of specific receptors on the surface of spleen cells, the effect of 2.5s nerve growth factor on 3H-thymidine uptake, cAMP and cGMP accumulation in mouse spleen lymphocytes has been studied. It was found that NGF added in vitro at the concentrations between 4 x 10(-7) and 4 x 10(-8) M significantly inhibited the incorporation of 3H-thymidine into lymphocytes DNA and increased cAMP levels in a dose-dependent manner but had no effect on cGMP levels. The maximal stimulation of cAMP synthesis occurred between 5 and 30 min after the NGF addition to the culture medium. When NGF was administered in vivo a significant dose-dependent inhibition of the lymphocytes proliferation was observed. These results indicate that an early increase of cAMP concentration is responsible for the antiproliferative action of NGF on mouse spleen lymphocytes and suggest that NGF could play an important role in the regulation of immune system function.     

Cyclosporine causes sympathetically mediated elevations in arterial pressure in rats

Cyclosporine-induced immunosuppression has emerged as a new cause of hypertension, but the underlying mechanisms are poorly understood. In patients, this hypertension is accompanied by sympathetic neural activation. We therefore hypothesized that increased sympathetic nerve discharge is an important mechanism by which cyclosporine raises blood pressure. To test this hypothesis, we examined effects of acute administration of cyclosporine (5 mg/kg i.v.) or vehicle on renal and lumbar sympathetic nerve activity, renal and femoral blood flow velocity (pulsed Doppler flowmetry), and arterial pressure in chloralose-anesthetized rats. Vehicle had no effect on sympathetic nerve activity, whereas cyclosporine caused renal and lumbar sympathetic nerve activity to increase progressively over 60 minutes to levels that were 362 +/- 46% and 388 +/- 70%, respectively, of the baseline values (p less than 0.05). These increases in sympathetic nerve activity were accompanied by proportional increases in renal and femoral vascular resistance and sustained increases in mean arterial pressure (+19 +/- 3 mm Hg, p less than 0.05 versus baseline). The cyclosporine-induced increases in regional vascular resistance and arterial pressure were greatly attenuated, or abolished, by ganglionic blockade or by clonidine (central sympatholysis) but were unaffected by angiotensin converting enzyme inhibition. These findings demonstrate that in an anesthetized animal preparation, the vasoconstrictor and blood pressure-raising effects of cyclosporine are caused by sympathetic neural activation.     

Involvement of arachidonic acid cascade pathways in interleukin-6-stimulated corticotropin-releasing factor release in vitro.

We have demonstrated that centrally administered interleukin-6 (IL-6) stimulates adrenocorticotropin (ACTH) secretion by a direct effect on corticotropin-releasing factor (CRF) release from the hypothalamus. Since metabolites of the arachidonic acid cascade (AAC) have been implicated in mediating actions of cytokines in different tissues and some AAC inhibitors were able to block pyrogenic effects of cytokines and suppress IL-1-induced ACTH secretion, we decided to examine the mechanism of IL-6 action on CRF release in vitro. After a 60-min preincubation in Krebs-Ringer bicarbonate buffer, medial basal hypothalami (MBH) were preincubated for 30 min with dexamethasone (DEX), a phospholipase A2 (PLA2) inhibitor, to block arachidonic acid (AA) formation, or with inhibitors of AA metabolism: a cyclooxygenase inhibitor--indomethacin (IND); a lipoxygenase inhibitor--5,8,11-eicosatriynoic acid (ETI), and an epoxygenase inhibitor--clotrimazole (CLO). Then, the medium was discarded and MBH were incubated with medium or the above compounds and/or IL-6 for 30 min, and CRF release into the incubation medium was measured by radioimmunoassay. As reported previously, 10(-13) M IL-6 increased CRF release, which was significantly suppressed by DEX in a dose-dependent manner. The suppression was already highly significant at a concentration of 10(-11) M DEX and became maximal at 10(-7) M, at which concentration CRF release was no longer stimulated by IL-6. The response to IL-6 was completely blocked at the highest DEX concentration evaluated (10(-5) M). CLO also suppressed IL-6-induced CRF release with a minimal effective dose of 10(-9) M. Suppression was complete at 10(-7) and 10(-5) M.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effect of calcium channel blockers on proliferation of human glioma cells in vitro

The effects of 2 specific calcium channel blockers, verapamil and nimodipine, on the proliferation of human glioma tumour cells were investigated in vitro. Tumour tissues for primary cell cultures were obtained bioptically from 3 patients with the histopathological diagnosis of glioblastoma. The [3H]-thymidine incorporation into glioma tumour cells DNA was used as a sensitive index of the cell proliferation. It was found that verapamil (10(-4)-10(-5) M) and nimodipine (10(-4)-10(-6) M) significantly inhibited the [3H]-thymidine uptake in a dose-related manner. The inhibitory effect of both calcium channel antagonists was reversed by simultaneous addition of calcium chloride (5 x 10(-3) M). These results indicate that verapamil and nimodipine may exert an antiproliferative effect on glioma cells growth acting through a blockade of specific voltage-dependent calcium channels.     

Implementing early infant diagnosis of HIV infection at the primary care level: experiences and challenges in Malawi

Problem

Malawi’s national guidelines recommend that infants exposed to the human immunodeficiency virus (HIV) be tested at 6 weeks of age. Rollout of services for early infant diagnosis has been limited and has resulted in the initiation of antiretroviral therapy (ART) in very few infants.

Approach

An early infant diagnosis programme was launched. It included education of pregnant women on infant testing, community sensitization, free infant testing at 6 weeks of age, active tracing of HIV-positive infants and referral for treatment and care.

Local setting

The programme was established in two primary care facilities in Blantyre, Malawi.

Relevant changes

Of 1214 HIV-exposed infants, 71.6% presented for early diagnosis, and 14.5% of those who presented tested positive for HIV. Further testing of 103 of these 126 apparently HIV-positive infants confirmed infection in 88; the other 15 results were false positives. The initial polymerase chain reaction testing of dried blood spots had a positive predictive value (PPV) of 85.4%. Despite active tracing, only 87.3% (110/126) of the mothers of infants who initially tested positive were told their infants’ test results. ART was initiated in 58% of the infants with confirmed HIV infection.

Lessons learnt

Early infant diagnosis of HIV infection at the primary care level in a resource-poor setting is challenging. Many children in the HIV diagnosis and treatment programme were lost to follow-up at various stages. Diagnostic tools with higher PPV and point-of-care capacity and better infrastructures for administering ART are needed to improve the management of HIV-exposed and HIV-infected infants.