Using mobile clinics to deliver HIV testing and other basic health services in rural Malawi.

CONTEXT: The majority of Malawians are impoverished and primarily dependant on subsistence farming, with 85% of the population living in a rural area. The country is highly affected by HIV and under-resourced rural health centers struggle to meet the government's goal of expanding HIV testing, antiretroviral treatment, and other basic services. ISSUE: This report describes the work of two four-wheel drive mobile clinics launched in 2008 to fill an identified service gap in the remote areas of Mulanje District, Malawi. The program was developed by an international non-governmental organization, Global AIDS Interfaith Alliance (GAIA), and the Mulanje District Health Office, with funding from the Elizabeth Taylor HIV/AIDS Foundation. The clinics provide: (1) rapid HIV testing and treatment referral; (2) diagnosis and treatment of malaria; (3) sputum collection for TB screening; (4) diagnosis and treatment of sexually transmitted and opportunistic infections; and (5) pre-natal care. The clinic vehicles provide medical supplies and personnel (a clinical officer, nurse, and nurse aide) to set up clinics in community buildings such as churches or schools. LESSONS LEARNED: In such a project, the implementation process and schedule can be affected by medication, supply chain and infrastructural issues, as well as governmental and non-governmental requirements. Timelines should be sufficiently flexible to accommodate unexpected delays. Once established, service scheduling should be flexible and responsive; for instance, malaria treatment rather than HIV testing was most urgently needed in the season when these services were launched. Assessing the impact of healthcare delivery in Malawi is challenging. Although mobile clinic and the government Health Management Information System (HMIS) data were matched, inconsistent variables and gaps in data made direct comparisons difficult. Data collection was compromised by the competing demand of high patient volume; however, rather than reducing the burden on existing health centers, the data suggest that the mobile clinics provided services for people who otherwise may not have attended a health center. The GAIA mobile clinics were integrated into a catchment area through a community participation model, allowing point-of-care primary health services to be provided to thousands of people in remote rural villagers. Strong relationships have been forged with local community leaders and with Malawi Ministry of Health officers as the foundation for long-term sustainable engagement and eventual integration of services into Health Ministry programs.

The association between the PTPN22 1858C>T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies.

The single nucleotide polymorphism 1858C>T in the PTPN22 gene is associated with type 1 diabetes (T1D) in several populations. Earlier reports have suggested that the association may be modified by human leukocyte antigen (HLA), as well as by islet autoantibodies. In a large case-control study of Swedish incident T1D patients and controls, 0-34 years of age, we tested whether the odds ratio (OR) measure of association was dependent on HLA or autoantibodies against the islet autoantigens glutamic acid decarboxylase 65 kDa autoantibodies (GADA), insulin, islet antigen-2, or islet cell. The association between the carrier status of 1858C>T allele in PTPN22 (PTPN22(CT+TT)) and T1D was modified by HLA. In addition, in GADA-positive T1D, the OR was 2.83 (2.00, 3.99), whereas in GADA-negative T1D, the OR was 1.41 (0.98, 2.04) (P for comparison=0.007). The OR of association between PTPN22(CT+TT) and GADA-positive T1D declined with increasing HLA-risk category from 6.12 to 1.54 (P=0.003); no such change was detected in GADA-negative T1D (P=0.722) (P for comparison=0.001). However, the absolute difference in risk between PTPN22(CC) and PTPN22(CT+TT) subjects with high-risk HLA was five times higher than that for subjects with low-risk HLA. We hypothesize that the altered T-cell function because of the PTPN22(1858C>T) polymorphism is exclusively associated with GADA-positive T1D at diagnosis.

Adaptive force control in grasping as a function of level of developmental disability.

BACKGROUND: The adaptation to the task demands of grasping (grip mode and object mass) was investigated as a function of level of developmental disability. METHODS: Subjects grasped objects of different grip widths and masses that were instrumented to record grip forces. RESULTS: Proportionally, fewer participants from the profound compared with moderate and severe disability groups were able to complete the prehensile tasks. Nevertheless, all participants who completed the task showed adaptive grasping behaviour in terms of level and variability of force produced. There was higher absolute and relative force variability in low mass tasks that was enhanced with greater level of developmental disability. CONCLUSIONS: The findings show task relevant adaptive grasping control with inhibition of force output at very-low-force conditions being the primary performance deficit of the profound disability group as a function of level of developmental disability.

IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

Age differences in noise and variability of isometric force production.

This study examined whether age-related improvements observed in the motor performance of children result from a reduction of noise in the output of the sensori-motor system. Children ages 6, 8, and 10 years and young adults (N = 48, 12 per group) performed continuous, constant isometric force contractions with the index finger at four different force levels with and without visual feedback. The results revealed that: (a) performance improved with increases in age, (b) the force output signal exhibited increased irregularity and a more broadband frequency profile with increases in age under conditions with feedback, and (c) there were no age differences in the irregularity of the force signal and smaller age differences in the frequency profiles under conditions without feedback. It is proposed that the age-related enhancements in performance throughout childhood are primarily due to a more appropriate mapping of the organization of the sensori-motor system to the task constraints rather than to reduction of system noise.

On learning to move randomly.

In 2 experiments, the authors examined whether and to what degree young adults can learn to produce random planar motion of the index finger or fingers. Three different types of information feedback were provided to the participants (N = 8 in each experiment) over up to 5 days of practice across the 2 experiments. The results from both experiments revealed that the participants produced a relatively low level of movement randomness in finger motion and that they did not learn through practice to enhance the stochastic properties of their movement under any feedback conditions. The findings provide further evidence that there are relatively tight constraints on the number of dimensions that are regulating single-limb planar motion and that those constraints are not susceptible to change through typical learning protocols.

Dynamics of self-injurious behaviors.

Self-injurious behavior was examined in a case study of head-banging by an 8-year-old girl with profound mental retardation and an autistic disorder. Trajectories of the arm movements and impact forces of the head blows were determined from a dynamic analysis of videotapes. Results revealed a high degree of cycle-to-cycle consistency in the qualitative dynamics of the limb motions, with one hand motions being faster than those with two hands (inphase and antiphase) and the motions with the helmet about 25% faster than those without the helmet. The impact force of SIBs as a percentage of body weights are near the low end of forces generated in boxing blows and karate hits.

Novel technetium (III)-Q complexes for functional imaging of multidrug resistance (MDR1) P-glycoprotein.

UNLABELLED: Overexpression of the multidrug resistance (MDR1) P-glycoprotein (Pgp) correlates with cancer chemotherapeutic failure. Lipophilic cationic radiopharmaceuticals such as 99mTc-sestamibi, 99mTc-tetrofosmin and 99Tc-furifosmin (Tc-Q12) have been validated as transport substrates for the MDR1 Pgp and may enable functional imaging of the MDR phenotype in cancer by observing enhanced washout rates of the tracers in those tumor areas expressing Pgp. To further explore and optimize the Pgp recognition properties of Schiff base phosphine mixed-ligand complexes of the Tc-Q series of nonreducible (Tc(III) cations, a variety of Tc-Q complexes were synthesized and tested in vitro for recognition as transport substrates by the human MDR1 Pgp. METHODS: Tracer assays with human drug-sensitive KB-3-1 epidermal carcinoma and MDR KB-8-5 cells expressing nonimmunodetectable and modest levels of MDR1 Pgp, respectively, were used to screen and pharmacologically characterize 37 novel 99mTc-Q analogs. RESULTS: The ideal agent should have low nonspecific binding, high distinction in net uptake between drug-sensitive cells and MDR tumor cells, and high enhancement of uptake in resistant cells after treatment with an MDR modulator, indicating selective blockade of Pgp-mediated efflux of the radiotracer. Three analogs, trans-[5,5'-(1,2-ethanediyldiimino)bis(2-OEt-2-Me-4-penten-3 -one)]bis[dimethyl(3-OMe-1-propyl)phosphine]99mTc(III) (99mTc-Q63) and two trans-[bis(methyl-bis(3-OMe-1-propyl)phosphine)] analogs (99mTc-Q57 and 99mTc-Q58) displayed transport distinctions between drug-sensitive and MDR cell lines that were equal to or greater than all previously available agents. Cyclosporin A, an MDR modulator, had no significant effect in KB-3-1 cells for these 99mTc-complexes but enhanced tracer accumulations in KB-8-5 cells with IC50 values of approximately 1 microM. In contrast, the non-MDR agents methotrexate and cisplatin had no effect on accumulation of 99mTc-Q complexes and 99mTc-sestamibi in KB-8-5 cells. CONCLUSION: Technetium-99m-Q57, 99mTc-Q58 and 99mTc-Q63 are avid transport substrates recognized by the human MDR1 Pgp, and have enhanced in vitro properties that may enable functional imaging of Pgp in vivo with improved signal-to-noise ratios and tissue contrast compared to currently available agents.

Limited joint mobility of the ankle in diabetic patients with cutaneous sensory deficit.

Limited joint mobility (LJM) of the ankle joint was measured in 48 diabetic patients classified into three groups: Insulin-dependent diabetes mellitus (IDDM = 15), non-insulin diabetes mellitus (NIDDM = 12) and patients with cutaneous sensory deficit in the foot (CD = 21). Specifically, plantar flexion, dorsiflexion and total range of motion was measured on both feet using goniometric techniques during active and passive movement conditions. No significant bilateral differences were established, therefore values for the right foot were used for statistical analyses. Diabetic patients were matched to 48 non-diabetic controls for age, weight and gender factors. A Semmes-Weinstein monofilament test was used on both feet to assess the integrity of cutaneous sensitivity in all patient and control subjects. Cutaneous sensory deficit patients (CD) had monofilament values greater than two standard deviations below control group mean values. There were no significant differences between the monofilament test values for the IDDM and NIDDM patients and control group data. LJM results indicated both plantar flexion and range of motion in CD patients under active and passive movement conditions were significantly reduced compared to control group data. No differences were observed for any pairwise comparisons between the IDDM and NIDDM groups compared to controls. The data is discussed in terms of the interaction between LJM in the foot and type of diabetic classification.

Marriage in Islam by Begum Habibullah (1883-1975).

PIP: This article identifies some of India's key legislative acts, reform measures, and Islamic laws on marriage in India and reports a speech in support of the Sarda Act that was passed in 1929. The speech was delivered by Begum Habibullah at the annual meeting of the Oudh Women's Social and Educational Conference. She was married to a landed family, and her husband was educated in England and a member of the civil service. She founded a school for Muslim girls and was elected in 1937 to the provincial legislative assembly. Social reforms were promulgated during 1920-47 among the legislatures of India. Many reforms changed Hindu laws, and some targeted women of all communities. Many reforms addressed child marriage and women's rights with regard to marriage, divorce, and inheritance. The impact of these reforms manifested itself in the stimulation of discussion of gender issues. The Age of Consent Committee in 1928 included mostly Indians and two women. The Committee collected evidence across the country of the prevalence and effects of child marriage. The Committee report concluded that child marriage in India affected about 40% of girls. Child marriage at ages under 15 years was most prevalent in Bengal, Bihar, and Orissa states, followed by the Central provinces and Berar and Bombay. Child marriage was more prevalent among Hindus than Muslims. Liberals tended to oppose child marriage, while religious Hindus and Muslims and conservatives tended to oppose restrictions to child marriage. The bill to regulate marriage age was introduced in 1929. The Sarda Act made it illegal to marry under the age of 14 years for girls and 18 years for boys. The Act was supported by women's groups. Begum's views were indicative of views of the time regarding the concern for women. She stressed the Act's complementarity to Islamic law.^ieng

The placebo effect.

The placebo effect will have a growing importance in the field of nuclear medicine as the potentials for palliative therapy with internal sources are realized. It is important for nuclear medicine physicians and their colleagues to be familiar with the role of placebo responses in clinical trials, especially when such trials involve the subjective assessment of pain. A summary of the literature on the placebo effect in pain studies is presented in which traditional values for placebo responses are contrasted with more current thinking in the field. The few published double-blind studies of pain relief after treatment with radiotherapeutic agents are summarized specifically with respect to their cited placebo response.

Sonographic visualization of the ovaries throughout pregnancy.

OBJECTIVE: To determine the frequency with which one or both normal ovaries can be visualized during a routine obstetric ultrasound examination. METHODS: The population consisted of 5617 pregnant women at 5.0-39.9 weeks' gestation, studied cross-sectionally. The sonographic visualization rate for one or both normal ovaries, as well as their position above or below the level of the umbilicus, was recorded for one examination in each patient. RESULTS: The study population was divided into three groups according to gestational age: first trimester, 5.0-12.9 weeks; second trimester, 13.0-26.9 weeks; and third trimester, 27.0-39.9 weeks. There were 829, 3195, and 1593 women in the first, second, and third trimesters, respectively. Most women were examined transvaginally in the first trimester; transabdominal sonography was used in the second and third trimesters. The ability to visualize one or both ovaries declined significantly (P < .05) from the first trimester to the second, as well as from the second trimester to the third (P < .001). The percentage of ovaries that were visualized above the umbilicus increased from 2.4% in the first trimester to 10.1% in the second trimester (P < .001), and to 21.7% in the third trimester (P < .001). CONCLUSION: As gestational age advances, there is a significant reduction in the ultrasound visualization rate of normal ovaries. This investigation provides normative data for ovarian visualization throughout pregnancy that may be helpful in establishing ultrasound laboratory standards.

Human biodistribution, dosimetry and clinical use of technetium(III)-99m-Q12.

UNLABELLED: Technetium(III)-99m-Q12, trans-(1,2-bis(dihydro-2,2,5,5-tetramethyl- 3(2H)furanone-4-methyleneimino)ethane)bis(tris(3-methoxy-1-propyl) - phosphine)technetium(III)-99m, is a nonreducible complex of Tc(III) which is herein evaluated as a myocardial perfusion imaging agent. METHODS: The biodistribution and dosimetry of 99mTc-Q12 were assessed in 10 normal volunteers, while its potential clinical use was evaluated in 70 patients. RESULTS: Safety parameters measured up to 24 hr postinjection demonstrate no clinically significant drug-related adverse reactions. Technetium(III)-99m-Q12 exhibits good heart uptake (2.2% injected dose at 1 hr postinjection under resting conditions) and no detectable myocardial washout or redistribution up to 5 hr postinjection. The biodistribution is characterized by very rapid hepatobiliary clearance which allows effective myocardial imaging at times as short as 15 min postinjection. Blood and plasma clearances and myocardial uptake are rapid, while lung uptake is minimal. The heart-to-lung and heart-to-liver ratios are higher at stress than at rest, independent of the time elapsed between injection and image acquisition, and independent of whether the patient is fasted or fed after tracer administration. A preliminary correlation shows that 46/47 patients with angiographically demonstrated CAD also have perfusion defects demonstrated by 99mTc-Q12. CONCLUSIONS: On the basis of the studies reported herein, 99mTc-Q12 appears to be a promising myocardial perfusion imaging agent.

Radiation synovectomy revisited.

Radiation synovectomy is a potential weapon in the therapeutic armamentarium of nuclear medicine. It is an attractive alternative to surgical or chemical synovectomy for the treatment of rheumatoid arthritis. In this article the clinical results obtained with radiation synovectomy from the 1950s through 1992 are summarized and reviewed. Even after taking into account the paucity of well-controlled trials and rigorous clinical follow-up, it is clear that radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis. However, the procedure is not widely used because of concerns about leakage of radioactivity from the treated joint, and the resulting high doses that can be delivered to nontarget organs. New approaches to the preparation of radiolabeled particles for use in radiation synovectomy promise to minimize this leakage and thus allow the full potential of this important radiotherapy to be realized.

Chemistry and biological behavior of samarium-153 and rhenium-186-labeled hydroxyapatite particles: potential radiopharmaceuticals for radiation synovectomy.

Hydroxyapatite (HA), a natural constituent of bone, was studied as a particulate carrier for beta-emitting radionuclides in radiation synovectomy. Particles were radiolabeled with 153Sm or 186Re and their in vivo safety was investigated following intra-articular injection into knees of normal rabbits and rabbits with antigen-induced arthritis (AIA). Radiolabeling efficiency was greater than 95%; in vitro studies showed minimal (< or = 1%) loss of activity from particles over a 6-day period with 153Sm-labeled HA and about 5% loss of activity over a 5-day period with 186Re-labeled HA. The total cumulative extra-articular leakage of 153Sm over 6 days was 0.28% in normal rabbits and 0.09% in AIA rabbits. Leakage of 186Re from the joint was 3.05% over a 4-day period with 80% of extra-articular activity found in the urine. Histopathological evaluation of treated knees showed that HA particles are distributed throughout the synovium, embedded in the synovial fat pad. The ease and efficiency with which this HA carrier is labeled, coupled with observed extremely low leakage rates from the joint, make radiolabeled HA particles an attractive candidate as a radiation synovectomy agent for evaluation in rheumatoid arthritis patients.

Synthesis and renal excretion of technetium-99m-labeled organic cations.

Organic cations are excreted more efficiently than organic anions in uremia suggesting superiority as renal imaging agents. In this study, three 99mTc-labeled cationic cyclam complexes were synthesized and their renal clearance quantified in rats. The complexes are cleared at a rate of about 2.5-3 times that of inulin and about 60% that of p-amino-hipurate. Inhibition of 99Tc-cyclam excretion by quinine indicates transport by the organic cation process. Comparative in vivo imaging experiments demonstrated that in normal rats 99mTc-cyclam reached peak renal activity 1.8 +/- 0.6 min after injection, a value intermediate between that for [131I]OIH (1.0 +/- 0) and 99mTc-MAG3 (2.8 +/- 0.6). In rats injected with the acute nephrotoxin cisplatin, the times to peak were lengthened with the relative order being 99mTc-cyclam > 99mTc-MAG3 > [131I]OIH. The results demonstrate that cationic complexes may be useful for renal imaging diagnostic applications.

Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous metastases.

Rhenium-186 (tin)hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in skeletal metastases in patients with advanced cancer. A single intravenous administration of approximately 34 mCi (1,258 MBq) resulted in significant improvement in pain in 33 of 43 evaluable patients (77%) following the initial injection, and in 7 of 14 evaluable patients (50%) following a second treatment. Patients responding to treatment experienced an average decrease in pain of about 60%, with one in five treatments resulting in a complete resolution of pain. The only adverse clinical reaction was the occurrence after about 10% of the administered doses of a mild, transient increase in pain within a few days following injection. Statistically significant but clinically unimportant decreases in total white blood cell counts and total platelet counts were observed within the first 8 weeks following the injection; no other toxicity was apparent. Rhenium-186(Sn)HEDP is a useful new compound for the palliation of painful skeletal metastases.

Area changes in slices of rat brain during preparation for histology or electron microscopy.

Cerebral slices cut from rat brain, either 2-3 mm or 0.27 mm thick, were used to study the effect of embedding and freezing. Paraffin wax sections 6 micrometer thick were mounted and stained with haematoxylin and eosin or Marsland et al.'s (1954) silver stain, and their areas were examined at each step. Embedding in paraffin wax of slices 2-3 mm thick, or in Epon of slices 0.27 mm thick, caused a diminution of their areas by 20-30%. Staining of paraffin wax sections did not alter their areas. Glycerol alone at 15% concentration had no effect on the areas, but at 30% concentration they were diminished by approximately 20%. Diminution of the areas of glycerol treated slices 0.27 mm thick also occurred when they were transferred to liquid N2 or to isopentane, but the areas increased after glycerol was replaced by Freon 12. It was concluded that embedding or freezing cerebral slices caused changes in their areas, but that staining of sections after they had been embedded, sectioned and mounted did not.