Frequencies of thalassemia in American blacks

The frequency of thalassemia was determined in a group of 541 healthy adult black males. Individuals with decreased mean corpuscular hemoglobin (MCH) values were evaluated further with hemoglobin analysis, iron studies, and globin chain synthesis. Of the males screened, 13.4% had MCH levels below 27.0 pg, while 1.4% had heterozygous beta thalassemia, 2.3% had iron deficiency, and 5.7% had globin synthesis findings compatible with the diagnosis of alpha thalassemia trait (alpha thalassemia-1). This study suggests that thalassemia is one of the most frequent hematologically depictable abnormalities in American blacks.     

Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2

OBJECTIVE: To estimate the prevalence and social correlates of cardiovascular disease. DESIGN: Population-based cross-sectional survey. Survey data were obtained through a standardized home interview and a clinic visit by trained nurses. The question sequence of the London School of Hygiene (the Rose Questionnaire) was used to identify the presence of definite angina, possible infarction, definite infarction, intermittent claudication and stroke. SETTING: Eight urban communities and rural areas in Saskatchewan in 1990. PARTICIPANTS: A probability sample of 2167 noninstitutionalized men and women aged 18 to 74 years who participated in the Saskatchewan Heart Health Survey. MAIN OUTCOME MEASURES: Prevalence of cardiovascular diseases. RESULTS: Among men, the prevalence of definite angina increased gradually with age from 1.7% (95% CI 0.6% to 2.7%) in the 18 to 34 year group, 3.8% (1.3% to 6.0%) in the 35 to 54 year group to 4.8% (2.8% to 8.3%) in the 55 to 74 year group, while the prevalence among women ranged from 2.5% (1.2 to 3.7%), 4.0% (1.6% to 6.5%) to 7.1% (5.1% to 11.6%) in these same age groups. The prevalence of possible angina, definite infarction, possible infarction and intermittent claudication increased with age as well, being higher in men than in women. Generally, the conditions were more prevalent among those with less education, lower income and those who were unemployed. CONCLUSIONS: These findings indicate that there is sociodemographic inequality in the prevalence of these manifestations of cardiovascular disease, and there is a need for in-depth qualitative research into causal factors in this relationship and for targeted programs of health promotion.     

Lumbar spinal root compression caused by Brucella granuloma

Myospherulosis is a rare condition. The authors report a unique case of this entity arising in paranasal sinus. The review of literature with emphasis on pathogenesis is also discussed.     

In vivo bioavailability and metabolism of topical diclofenac lotion in human volunteers

OBJECTIVE: To characterize the long-term impact of four hormone therapy regimens on insulin and glucose concentrations measured during a standard oral glucose tolerance test. RESEARCH DESIGN AND METHODS: The Postmenopausal Estrogen/Progestin Intervention Study was a 3-year placebo-controlled randomized trial to assess effects of four hormone regimens on cardiovascular risk factors. This efficacy analysis describes glucose and insulin concentrations from 788 adherent women at baseline and at 1 and 3 years' postrandomization. RESULTS: When compared with women taking placebo, those taking conjugated equine estrogen (CEE) at 0.625 mg/day with or without a progestational agent had mean fasting insulin levels that were 16.1% lower, mean fasting glucose levels 2.2 mg/dl lower, and mean 2-h glucose levels 6.4 mg/dl higher (each nominal P < 0.05). No significant differences were apparent between women taking CEE only versus the three progestin regimens: medroxyprogesterone acetate (MPA) at 2.5 mg daily (continuous MPA), MPA at 10 mg on days 1-12 (cyclical MPA), and micronized progesterone (MP) (cyclical) at 200 mg on days 1-12. The impact of hormone therapy on insulin and glucose depended on baseline levels of fasting insulin and 1-h glucose (P < 0.05). However, the treatment effects on carbohydrate metabolism appeared to be consistent across participant subgroups formed by lifestyle, clinical, and demographic characteristics. CONCLUSIONS: Oral hormone therapy involving 0.625 mg/day of CEE may modestly decrease fasting levels of insulin and glucose. Postchallenge glucose concentrations are increased, however, which may indicate delayed glucose clearance.     

Increased in vivo collagen synthesis and in vitro cell proliferative effect of glycolic acid

BACKGROUND: Glycolic acid treatment is believed to reverse the photoaging process by increasing collagen synthesis in the skin. However, this effect has not been clearly defined even though alpha hydroxy acid products are used extensively. OBJECTIVE: This study aimed to define the primary effect of glycolic acid on collagen synthesis that may be achieved by functional activation or proliferation of fibroblasts. METHODS: Glycolic acid treatment was compared in vivo with lactic acid (hairless mice) and in vitro to malic acid (normal human skin fibroblast culture) with controls. To find the functional activation of fibroblasts, Northern blot assay for type I collagen synthesis with histometric analysis (in vivo) was performed. Cell proliferation assay (MTT) with procollagen type I C-peptide (PICP) enzyme immunoassay and radioisotope ([3H]proline) incorporated collagen production from cultured fibroblasts were determined. RESULTS: The in vivo collagen mRNA expression with histometric analysis revealed greater collagen synthesis by glycolic acid compared with lactic acid and control. In vitro cell proliferative effect of glycolic and greater amount of collagen production showed a steady increase in a dose-dependent manner. CONCLUSION: Both in vivo and in vitro, glycolic acid treatment increased the production of collagen and fibroblast proliferation. These effects may be the mechanism by which glycolic acid reverses the process of photoaging.     

Hippocampal AMPA and NMDA mRNA levels and subunit immunoreactivity in human temporal lobe epilepsy patients and a rodent model of chronic mesial limbic epilepsy

This study compared temporal lobe epilepsy patients, along with kindled animals and self sustained limbic status epilepticus (SSLSE) rats for parallels in hippocampal AMPA and NMDA receptor subunit expression. Hippocampal sclerosis patients (HS), non-HS cases, and autopsies were studied for: hippocampal AMPA GluR1-3 and NMDAR1&2b mRNA levels using in situ hybridization: GluR1, GluR2/3, NMDAR1, and NMDAR2(a&b) immunoreactivity (IR); and neuron densities. Similarly, spontaneously seizing rats after SSLSE, kindled rats, and control animals were studied for: fascia dentata neuron densities: GluR1 and NMDAR2(a&b) IR; and neo-Timm's staining. In HS and non-HS cases, the mRNA hybridization densities per granule cell, as well as molecular layer IR, showed increased GluR1 (relative to GluR2/3) and increased NMDAR2b (relative to NMDAR1) compared to autopsies. Likewise, the molecular layer of SSLSE rats with spontaneous seizures demonstrated more neo-Timm's staining, and higher levels of GluR1 and NMDAR2(a&b) IR compared to kindled animals and controls. These results indicate that hippocampal AMPA and NMDA receptor subunit mRNAs and their proteins are differentially increased in association with spontaneous, but not kindled, seizures. Furthermore, there appears to be parallels in fascia dentata AMPA and NMDA receptor subunit expression between HS (and non-HS) epileptic patients and SSLSE rats. This finding supports the hypothesis that spontaneous seizures in humans and SSLSE rats involve differential alterations in hippocampal ionotrophic glutamate receptor subunits. Moreover, non-HS hippocampi were more like HS cases than hippocampi from kindled animals with respect to glutamate receptors; therefore, hippocampi from kindled rats do not accurately model human non-HS cases, despite some similarities in neuron densities and mossy fiber axon sprouting.     

Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar)

A potential mechanism of chemotherapy resistance in acute myeloid leukemia (AML) is the multidrug resistance (MDR-1) gene product P-glycoprotein (P-gp), which is often overexpressed in myeloblasts from refractory or relapsed AML. In a multicenter phase II clinical trial, 37 patients with these poor risk forms of AML were treated with PSC 833 (Valspodar; Novartis Pharmaceutical Corporation, East Hanover, NJ), a potent inhibitor of the MDR-1 efflux pump, plus mitoxantrone, etoposide, and cytarabine (PSC-MEC). Pharmacokinetic (PK) interactions of etoposide and mitoxantrone with PSC were anticipated, measured in comparison with historical controls without PSC, and showed a 57% decrease in etoposide clearance (P =.001) and a 1.8-fold longer beta half-life for mitoxantrone in plasma (P <.05). The doses of mitoxantrone and etoposide were substantially reduced to compensate for these interactions and clinical toxicity and in Cohort II were well tolerated at dose levels of 4 mg/m2 mitoxantrone, 40 mg/m2 etoposide, and 1 g/m2 C daily for 5 days. Overall, postchemotherapy marrow hypoplasia was achieved in 33 patients. Twelve patients (32%) achieved complete remission, four achieved partial remission, and 21 failed therapy. The PK observations correlated with enhanced toxicity. The probability of an infectious early death was 36% (4 of 11) in patients with high PK parameters for either drug versus 5% (1 of 20) in those with lower PK parameters (P =.04). P-gp function was assessed in 19 patients using rhodamine-123 efflux and its inhibition by PSC. The median percentage of blasts expressing P-gp was increased (49%) for leukemic cells with PSC-inhibitable rhodamine efflux compared with 17% in cases lacking PSC-inhibitable efflux (P =.004). PSC-MEC was relatively well tolerated in these patients with poor-risk AML, and had encouraging antileukemic effects. The Eastern Cooperative Oncology Group is currently testing this regimen versus standard MEC chemotherapy in a phase III trial, E2995, in a similar patient population.     

Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations

BACKGROUND: It has previously been shown that a combination of erythromycin and benzoyl peroxide is superior to either ingredient when used alone in the treatment of acne. A clindamycin/benzoyl peroxide combination gel might have an advantage over erythromycin/benzoyl peroxide gel because the former does not require refrigeration after it is dispensed. OBJECTIVE: Our purpose was to determine the efficacy and safety of a combination clindamycin/benzoyl peroxide gel when compared with benzoyl peroxide, clindamycin, or vehicle gels. METHODS: In two double-blind, randomized, parallel, vehicle-controlled trials, patients were treated for 11 weeks with once-nightly application of one of the above preparations. Evaluations were performed at 2, 5, 8, and 11 weeks and included lesion counts and assessment of global responses and irritant effects. RESULTS: A total of 334 patients completed the study. All three active preparations were significantly superior to the vehicle in global improvement and in reducing inflammatory lesions and noninflammatory lesions. The combination gel was significantly superior to the two individual agents in global improvement and reduction of inflammatory lesions and also to the clindamycin gel in reducing noninflammatory lesions. There was no significant difference in tolerance to the active gels versus the vehicle gel. CONCLUSION: In the treatment of acne, topical clindamycin/benzoyl peroxide combination gel is well tolerated and superior to either individual ingredient.     

Evaluation of plain abdominal radiographs in the diagnosis of abdominal pain

In an effort to develop referral criteria for the ordering of abdominal radiographs for patients presenting with abdominal symptoms, we prospectively studied the relation between clinical data and radiographic abnormalities. Of 1780 examinations, 179 (10.0%) showed some radiographic abnormality. If abdominal radiographs would have been limited to those patients who had moderate or severe abdominal tenderness, or to patients with a high clinical suspicion of bowel obstruction, renal or ureteral calculi, trauma, ischemia, or gallbladder disease, regardless of the degree of tenderness, 956 (53.7%) examinations would not have been done. All radiographic abnormalities reflecting a serious pathologic process would have been identified. Only 33 (3.5%) abnormalities of limited significance, almost all localized or generalized ileus, would have been undetected. The adoption of these referral criteria would result in minimal loss of clinically useful information, large financial savings, and a reduction in radiation exposure.