Controlled synthesis of dicalcium phosphate dihydrate (DCPD) from metastable solutions: insights into pathogenic calcification.

Calcium phosphate (CaP) compounds may occur in the body as abnormal pathogenic phases in addition to their normal occurrence as bones and teeth. Dicalcium phosphate dihydrate (DCPD; CaPO4·2H2O), along with other significant CaP phases, have been observed in pathogenic calcifications such as dental calculi, kidney stones and urinary stones. While other studies have shown that polar amino acids can inhibit the growth of CaPs, these studies have mainly focused on hydroxyapatite (HAp; Ca10(PO4)6(OH)2) formation from highly supersaturated solutions, while their effects on DCPD nucleation and growth from metastable solutions have been less thoroughly explored. By further elucidating the mechanisms of DCPD formation and the influence of amino acids on those mechanisms, insights may be gained into ways that amino acids could be used in treatment and prevention of unwanted calcifications. The current study involved seeded growth of DCPD from metastable solutions at constant pH in the presence of neutral, acidic and phosphorylated amino acid side chains. As a comparison, solutions were also seeded with calcium pyrophosphate (CPP; Ca2P2O7), a known calcium phosphate inhibitor. The results show that polar amino acids inhibit DCPD growth; this likely occurs due to electrostatic interactions between amino acid side groups and charged DCPD surfaces. Phosphoserine had the greatest inhibitory ability of the amino acids tested, with an effect equal to that of CPP. Clustering of DCPD crystals giving rise to a "chrysanthemum-like" morphology was noted with glutamic acid. This study concludes that molecules containing an increased number of polar side groups will enhance the inhibition of DCPD seeded growth from metastable solutions.

Meta-analysis of the outcomes of Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) for inguinal hernia.

OBJECTIVES: To evaluate the outcomes of Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) in patients undergoing elective inguinal hernia repair. METHODS: In compliance with PRISMA statement standards, electronic databases were searched to identify all studies reporting the outcomes of TREPP in patients undergoing elective inguinal hernia repair. The outcomes of interest included recurrence, chronic pain, haematoma, and wound infection. Proportion meta-analysis model was constructed to quantify the risk of postoperative complications and direct comparison meta-analysis model was constructed to compare the outcomes of TREPP and other open techniques. Random-effects modelling was applied to calculate pooled outcome data. RESULTS: Seven studies enrolling 1891 patients undergoing TREPP were included. The mean operative time was 26 min (95% CI 15-36). Pooled analyses showed that TREPP was associated with 3.00% (95% CI 1.00-6.00%) risk of recurrence, 3.00% (95% CI 2.00-6.00%) risk of chronic pain, 8.00% (95% CI 0.00-20.00%) risk of haematoma, and 3.00% (95% CI 0.00-6.00%) risk of wound infection. The results remained consistent through subgroup analysis of patients with primary hernias and those with recurrent hernias. Analysis of a limited number of comparative studies showed no difference between TREPP and Lichtenstein technique in terms of recurrence (OR 1.57, P = 0.26) and chronic pain (OR 1.16, P = 0.59). CONCLUSIONS: The best available evidence suggests that TREPP may be a promising technique for elective repair of inguinal hernias as indicated by low risks of recurrence, chronic pain, haematoma, and wound infection. The available evidence is limited to studies from a same country conducted by almost the same research group which may affect generalisability of the findings. Moreover, there is a lack of comparative evidence on outcomes of TREPP versus other techniques highlighting a need for high-quality randomised controlled trials for definite conclusions. Although the available evidence is not adequate for definite conclusions, the results of current study can be used for sample size calculation and power analysis in future trials.

Characterization of a noncytopathic HIV-2 strain with unusual effects on CD4 expression.

A new isolate of the human immunodeficiency virus type 2, designated HIV-2UC1, was recovered from an Ivory Coast patient with normal lymphocyte numbers who died with neurologic symptoms. Like some HIV-1 isolates, HIV-2UC1 grows rapidly to high titers in human peripheral blood lymphocytes and macrophages and has a differential ability to productively infect established human cell lines of lymphocytic and monocytic origin. Moreover, infection with this isolate also appears to involve the CD4 antigen. However, unlike other HIV isolates, HIV-2UC1 does not cause cytopathic effects in susceptible T cells nor does it lead to loss of CD4 antigen expression on the cell surface. These results indicate that HIV-2 may be found in individuals with neurologic symptoms and that the biological characteristics of this heterogeneous subgroup can differ from those typical of HIV-1.

Preventing iatrogenic air embolism in the intensive care unit.

Air embolism is a potentially fatal consequence of incorrect connection of endotracheal tube cuff inflator devices. Currently, air lines from these devices can be connected to indwelling cannulae without impediment. This possibility can be eliminated with a simple modification of the air line, as described here.

HIV heterogeneity and viral pathogenesis.

HIV research in the past year has elucidated many questions relevant to strategies for treatment and control. For instance, there is a greater understanding of the diversity of HIV isolates as well as the wide range of potential cells sensitive to infection. The search for a safe, effective vaccine now calls for more caution in the light of the discovery of neutralization-resistant variants and antibody-mediated enhancement of infection. Efforts to control HIV must take into account the various mechanisms of virus entry into host cells, and the processes involved in cytopathic effects. Moreover, the role of cells of the mononuclear phagocyte system as reservoirs for HIV particles should be recognized. Together with new information about cytokine induction of HIV, the concept of latent infection of monocytes and macrophages has profound implications for virus persistence and dissemination, especially in the seronegative individual. While many factors about HIV have been uncovered in the past year, several questions remain unanswered and new ones have arisen. For instance, in how many ways does the virus kill in host cell? What causes latency and why does it occur in some but not all hosts? How can virus-filled macrophage vesicles be reached by therapeutic agents or prevented from releasing HIV? What surveillance mechanisms allow some productively infected hosts (cells as well as individuals) to survive beyond expectation? These and other questions should provoke future research on this presently complex and challenging pathogen.

Antibody-dependent cellular cytotoxicity is directed against both the gp120 and gp41 envelope proteins of HIV.

To define the target antigens for antibody-dependent cellular cytotoxicity (ADCC), assays were performed using affinity-purified human immunoglobulin (Ig) or polyclonal rabbit sera directed against specific proteins of HIV. ADCC was not found using affinity-purified anti-core (p25) human Ig or sera obtained from rabbits hyper-immunized with recombinant p25. However, when affinity-purified human Ig or rabbit antisera specific for the envelope glycoproteins, gp120 or gp41, were used in ADCC assays, killing of HIV-infected cells was observed. These results indicate that antibodies in the infected individual that mediate ADCC are directed against both the gp120 and gp41 HIV envelope proteins and not against the viral core protein.

Orienting therapists about patients' needs to increase patient satisfaction.

Twenty-nine psychotherapists received orientation about patients' cultural background, expectations, and therapeutic needs. They treated 98 patients before orientation and 73 afterward, and a follow-up interview was conducted 4-6 weeks after completion of therapy. The patients seen after therapist orientation were more satisfied with the services, felt better able to handle problems, were more likely to seek therapy for future problems, and felt more strongly that their needs for clinic services had been met than the patients seen by therapists before orientation. Analyses of therapist experience, patients' ethnicity, and patients' orientation to psychotherapy showed no significant interactions with patient satisfaction.

Human immunodeficiency virus recovery from bronchoalveolar lavage fluid in patients with AIDS.

We cultured bronchoalveolar lavage fluid for the human immunodeficiency virus (HIV) from 23 consecutive patients with acquired immunodeficiency syndrome (AIDS) and pulmonary symptoms. We also included a nonconsecutive AIDS patient with recent worsening of respiratory symptoms who had had lymphocytic interstitial pneumonitis (LIP) diagnosed six months earlier. Infectious HIV was present in the cellular fraction from two of the 23 consecutive patients and in the patient with LIP. No virus was isolated from the cell-free portion of the centrifuged fluids. The patients from whom HIV was cultured were not distinguishable from other patients by clinical, radiographic, or laboratory data, and their subsequent course did not appear to differ. One patient with a positive HIV culture had organizing pneumonia without evidence of LIP at autopsy three weeks after lavage. This study demonstrates that HIV can be cultured from cells obtained by bronchoalveolar lavage and suggests that its presence is not associated with a single specific pulmonary histologic pattern.

Advances in controlling hypertension in low-income patients.

Since hypertension is the foremost problem in minority and low-income populations treated in our community health centers, in 1976 we introduced a protocol that standardized diagnostic criteria and a step-care approach to the treatment of hypertension. In 1980, we modified the original protocol with guidelines for dietary management and an outline for improving physician-patient communication and health education. We hypothesized that implementing the protocol (and later modifications) would be associated with improved identification and control of hypertension. We conducted a cross-sectional study of hypertensive patients' charts in three community health centers in 1973, 1978, and 1982, and determined the status of blood pressure (BP) control of those patients by the end of the year. In 1973 (before protocol), 4 percent of hypertensives were undiagnosed and untreated, and 20 percent were lost to follow-up. Among those who remained under care, only 33 percent were under control (BP less than 160/95 mm Hg). In 1978, two years after the protocol was introduced, there were fewer undiagnosed and untreated patients (2 percent), but the number lost to follow-up increased to 31 percent. The proportion of hypertensives under control increased to 70 percent. In 1982, two years after the modifications to the protocol were introduced, the proportion of patients lost to follow-up decreased to 28 percent, and the proportion of patients with controlled blood pressure increased to 79 percent. The improved level of control was statistically significant at p less than .0001 (chi-square test).(ABSTRACT TRUNCATED AT 250 WORDS)

Osmotic drug delivery using swellable-core technology.

Swellable-core technology (SCT) formulations that used osmotic pressure and polymer swelling to deliver drugs to the GI tract in a reliable and reproducible manner were studied. The SCT formulations consisted of a core tablet containing the drug and a water-swellable component, and one or more delivery ports. The in vitro and in vivo performance of two model drugs, tenidap and sildenafil, formulated in four different SCT core configurations: homogeneous-core (single layer), tablet-in-tablet (TNT), bilayer, and trilayer core, were evaluated. In vitro dissolution studies showed that the drug-release rate was relatively independent of the core configuration but the extent of release was somewhat lower for the homogeneous-core formulation, particularly under non-sink conditions. The drug-release rate was slower with increasing coating thickness and decreasing coating permeability, and was relatively independent of the drug loading and the number and size of the delivery ports. The drug-release rates were similar for the two model drugs despite significant differences in their physicochemical properties. Tablet-recovery and pharmacokinetic studies conducted in beagle dogs showed that the in vivo release of drug from SCT formulations was comparable to the in vitro drug release.

Effects of ion transport inhibition on rat mandibular gland secretion.

The effects of substituting gluconate for extracellular Cl, and of treatment with various ion transport blockers, on cytosol pH (pHi) and secretion by the acetylcholine stimulated rat mandibular gland were studied in vitro. Gluconate replacement increased pHi from 7.12 +/- 0.02 to 7.27 +/- 0.04, caused secretory rate to fall by 75%, and increased salivary HCO3 from 14 +/- 0.9 mmol/L to 67 +/- 1.5 mmol/L. Furosemide (1 mmol/L), which blocks Na-K-2Cl symports and Cl-HCO3 antiports, had effects similar to those of gluconate replacement, except that secretion was reduced only by 59%. Bumetanide (1 mmol/L), which blocks only Na-K-2Cl symports, caused a 67% reduction in secretion rate, but it had little effect on pHi and caused only a small rise in salivary HCO3 concentration. SITS (1 mmol/L), which blocks Cl-HCO3 antiports, increased pHi to 7.26 +/- 0.03 and induced a small rise in the secretory rate. Methazolamide and acetazolamide (1 mmol/L), both of which inhibit carbonic anhydrase and may also block anion channels, increased pHi to 7.43 +/- 0.02 and 7.20 +/- 0.03, respectively, but had no effect on secretory rate, and reduced salivary HCO3 slightly. Ba (3 mmol/L), tetraethylammonium (10 mmol/L), and decamethonium (5 mmol/L) all caused marked but reversible reductions in secretory rate, consistent with the known actions of these agents on K channels. Ba, however, also appeared to act as a Ca antagonist, an action that it seemed to share with Mn ions (5 mmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluating sensory conflict and postural instability. Theories of motion sickness.

Two experiments were carried out to evaluate the sensory conflict and the postural instability theories of motion sickness. The central hypothesis of sensory conflict theory is that motion sickness is caused by conflict between the current pattern of sensory inputs about self-movement and the pattern that is expected on the basis of previous experience. A subsidiary hypothesis is that the degree of motion sickness is proportional to the magnitude of sensory conflict. The central hypothesis of postural instability theory is that motion sickness is caused by loss of postural control. A subsidiary hypothesis is that the degree of motion sickness is proportional to amount of postural instability, which can be manipulated by physical restraint. In both experiments there were two levels of sensory conflict and two levels of postural restraint. Dependent variables were latency of onset and severity of motion sickness. The widespread occurrence of motion sickness in both experiments clearly confirmed the main hypothesis of sensory conflict theory. The results from Experiment 1, that there was significantly more motion sickness in the restrained condition, and from Experiment 2, that there was no significant difference in symptoms between the two restraint conditions, provide no support for the subsidiary hypothesis of postural instability theory. Evidence relating to the subsidiary proposition of sensory conflict theory was inconsistent.

PHA response and methylazoxymethanol acetate.

Several reports have indicated the mutagenicity of the cycasin aglycone, methyl azoxymethanol (MAM). Van Den Berg and Ball (1972) have demonstrated the inhibitory effects of MAM acetate (MAMac), a more stable form of the aglycone, on DNA synthesis and cell proliferation in HeLa cells. The purpose of this study was to observe the effects of MAMac on blastogenesis in the human short-term leucocyte culture system. A depression in blastogenesis by MAMac was observed cytologically derived from two individuals. The same effect was observed utilizing [3H] thymidine as an indicator of blastogenesis in a series of cultures from 11 male individuals exposed to varying doses of MAMac, ranging from 5 through 800 mug/ml.

Human sister chromatid exchange caused by methylazoxymethanol acetate.

The incidence of sister chromatid exchange was determined in human leucocyte cultures treated with methylazoxymethanol acetate. In all individuals examined, treated cultures manifested a significantly higher frequency of sister chromatid exchanges than controls. Two concentrations of MAM AC were tested in blood cultures from nine individuals. The concentrations varied from individual to individual since they were determined by means of individual dose-response curves, which involved [3H]-thymidine incorporation in PHA-stimulated short-term lymphocyte cultures versus MAM AC contraction. The lower concentration was less than the TD50 dose. Compared to control cultures, the lower concentration caused a higher incidence of sister chromatid exchange in eight of nine individuals. The cumulative mean value for all control cultures was 5.32 exchanges per cell while that for cultures treated with the higher concentration was 10.73.

Black and white differences: narrowing the gap in cancer medicine.

Excess mortality is a complex problem involving multiple sub-problems including culture, economics, lifestyle, issues related to cancer biology, and access to medical care among other issues. Consideration has to be given to the multiple influences that lead to this discrepancy in survival related to cancer and the increased incidence of certain tumors. Increased availability of state-of-the-art cancer treatment to the population as a whole will upgrade the level of care by those that participate in clinical trials; the physicians and finally even those patients who are not entered into the trials. Upgrading the access to information about prevention and control of cancer is of equal importance. There are those tumors with possible biological explanations for increases in cancer incidence in the Black population, in particular, multiple myeloma and prostate cancer. There are tumors which are increasing in incidence in this population with no explanation but which must relate to biological factors.

Stingray hickey.

A large number of injuries from stingrays are reported each year in the United States. Usually these injuries are inflicted by the stingray's tail, after the resting stingray is stepped on. The tail has a stinger that can cause puncture wounds with envenomation. We report a case in which an injury from a stingray was due to its bite.

Pseudofolliculitis barbae associated with an unusual hair whorl.

Descriptions of hair direction in the literature have emphasized unusual patterns of the scalp and associated developmental brain defects. We present the case of a white patient with unilateral pseudofolliculitis barbae associated with a hair whorl in the inframandibular region. To our knowledge, this is the first reported case of pseudofolliculitis barbae associated with a hair whorl.

A double-blind placebo controlled evaluation of acupressure in the treatment of motion sickness.

We used 36 subjects in a double-blind placebo controlled experiment to evaluate the effectiveness of acupressure as a prophylaxis against motion sickness. There were two independent variables with two levels each: acupressure vs. placebo, and motion sickness high vs. low susceptible subjects. The provocative stimulus was rotation about two orthogonal axes. Signs and symptoms of motion sickness were scored both by the subject and the observer. In spite of previous reports to the contrary, acupressure provided no protection against motion sickness for either high or low susceptible subjects.

Electrodermal activity as an index of motion sickness.

Sweating in the absence of thermal stimulation is one of the cardinal symptoms of motion sickness. But since sweating is closely related to electrodermal activity this may be a potentially useful index of the intensity of motion sickness. In order to evaluate this possibility, the correlations between electrodermal activity and a range of signs and symptoms of motion sickness were examined in four experiments, in which a total of 170 subjects were exposed to a cross-coupled force environment. Although increases in skin conductance did not correlate with specific single indices of motion sickness, correlations with a questionnaire based on several signs and symptoms varied from 0.89 (p less than 0.001) to 0.11 (N.S.). It is concluded that skin conductance potentially offers a valid and very precise measure of motion sickness, but that it is sensitive to extraneous factors only some of which are currently understood.

Comparison of three instruments in predicting accidental falls in selected inpatients in a general teaching hospital.

Accidental patient falls are becoming a major cause of concern for hospitalized inpatients. It is well known that patients who fall once during their hospital stay are more likely to fall again and that fall rates tend to be higher in hospitalized elderly individuals. Concerned health care team personnel recognize that many accidental patient falls may be predicted and, thus, prevented. The best tool to predict falls has not been determined yet. The purpose of this study was to compare the abilities of the Morse Fall Scale (MFS), the Functional Reach (FR) test, and the nurses' clinical judgment in predicting those inpatients on a rehabilitation unit and a geriatric medical ward who were most likely to fall. A total of 98 patients were screened in a 3-month period, with each patient undergoing all three instruments the same day. The results showed that the two objective standardized tests (i.e., MFS, FR) were time consuming and often inconvenient and were no better at prediction than the clinical judgments made by the primary nurses.