βS-Globin Gene Cluster Haplotypes in the West Bank of Palestine

Sickle cell disease is an inherited autosomal recessive disorder of the β-globin chain. In Palestine it is accompanied by a low level of Hb F (mean 5.14%) and a severe clinical presentation. In this study, 59 Palestinian patients, homozygotes for Hb S were studied for their haplotype background. Eight polymorphic sites in the β-globin gene cluster were examined. The Benin haplotype was predominant with a frequency of 88.1%, followed by a frequency of 5.1%?for the Bantu haplotype. One chromosome was found to carry the Cameroon haplotype (0.85%). Three atypical haplotypes were also found (5.95%). Heterogeneity was observed in Hb F production, ranging between 1.5 and 17.0%, whereas the ^Gγ ratio was homogeneous among all haplotypes with a normal amount of about 41%. Our results are in agreement with previous reports of the Benin haplotype origin in the Mediterranean.     

COL4A3/COL4A4 mutations producing focal segmental glomerulosclerosis and renal failure in thin basement membrane nephropathy

Mutations in the COL4A3/COL4A4 genes of type IV collagen have been found in approximately 40% of cases of thin basement membrane nephropathy, which is characterized by microscopic hematuria and is classically thought to cause proteinuria and chronic renal failure rarely. Here we report our observations of 116 subjects from 13 Cypriot families clinically affected with thin basement membrane nephropathy. These families first came to our attention because they segregated microscopic hematuria, mild proteinuria, and variable degrees of renal impairment, but a dual diagnosis of focal segmental glomerulosclerosis (FSGS) and thin basement membrane nephropathy was made in 20 biopsied cases. Molecular studies identified founder mutations in both COL4A3 and COL4A4 genes in 10 families. None of 82 heterozygous patients had any extrarenal manifestations, supporting the diagnosis of thin basement membrane nephropathy. During follow-up of up to three decades, 31 of these 82 patients (37.8%) developed chronic renal failure and 16 (19.5%) reached end-stage renal disease. Mutations G1334E and G871C were detected in seven and three families, respectively, and were probably introduced by founders. We conclude that these particular COL4A3/COL4A4 mutations either predispose some patients to FSGS and chronic renal failure, or that thin basement membrane nephropathy sometimes coexists with another genetic modifier that is responsible for FSGS and progressive renal failure. The findings presented here do not justify the labelling of thin basement membrane nephropathy as a benign condition with excellent prognosis.     

Association Between Widowhood and Risk of Diagnosis With a Sexually Transmitted Infection in Older Adults

Objectives. We assessed whether widowhood is associated with risk of diagnosis with a sexually transmitted infection (STI) among older adults in the United States and whether the associations observed in men differed before and after the introduction of sildenafil, the first oral erectile dysfunction medication approved by the Food and Drug Administration.Methods. We used Cox proportional hazards regression to analyze the time to first STI diagnosis in a random sample of married, Medicare-eligible couples aged 67 to 99 years in 1993 (N = 420 790 couples).Results. Twenty-one percent of male and 43% of female participants lost a spouse during the 9-year study period. Only 0.65% of men and 0.97% of women were diagnosed with an STI. Widowhood was associated with an increased risk of STI diagnosis for men only, with the largest effects found 0.5 to 1 year after a wife''s death. Effects for men were larger after the introduction of sildenafil.Conclusions. Widowhood in older men, but not women, increased the risk for STIs, especially in the postsildenafil era. Clinicians should address sexual health issues with older patients, especially bereaved men taking erectile dysfunction medications.Widowhood has been shown to be associated with numerous health outcomes, including depression, disability, health care usage, and all-cause and cause-specific mortality.^1–6 One issue that has not been explored is whether widowhood is associated with increased sexual risk-taking. This topic is important, because untreated sexually transmitted infections (STIs) increase the risk of contracting other STIs, including HIV infection, and in themselves constitute socially stigmatized and often painful avoidable morbidity. Moreover, the proportion of incident HIV cases that are among those aged 50 years and older has risen in recent years, thus raising the possibility of a corresponding increase in the prevalence of STIs generally among older persons.⁷The few studies that have looked at sexual risk-taking among older adults have documented a nonnegligible minority at risk for contracting STIs. For example, 1 national survey found that 5.5% of Americans aged 50 to 75 years reported having engaged in sexual behaviors identified as HIV risk factors, including 2.2% with multiple partnerships in the previous year. Yet fewer than 4% of older sexually active heterosexual risk-takers used condoms consistently during the preceding 6 months. In fact, in a subsample taken from high-HIV-risk cities, older risk-takers were only one sixth as likely to use condoms and one fifth as likely to have been tested for HIV as were risk-takers in their 20s.⁸ In another nationally representative study, 9% of persons aged 60 to 69 years and 8% of persons aged 70 years or older who were sexually active in the previous 5 years reported 2 or more partners during that period. In addition, 2% of married persons aged 60–69 years and 3.5% of married persons aged 70 or more years acknowledged an extramarital partnership in the past 5 years. Relative to younger age groups, older Americans with multiple partners were less likely to report consistent condom use or behavior change in response to the HIV/AIDS epidemic.⁹ Other studies have similarly documented low levels of condom use among sexually at-risk older persons.¹⁰ Although the precise efficacy of condoms among older persons is unknown, this failure to protect against STIs is especially worrisome given older women''s greater physiologic susceptibility to infection compared with younger women.¹⁰In the present study, we assessed whether widowhood is associated with increased sexual risk-taking by asking (1) Is widowhood associated with an increased risk of being diagnosed with an STI? (2) Does the association depend on the time that has elapsed since the spouse''s death? In addition, because the introduction of oral erectile dysfunction (ED) medications in 1998 expanded the realm of what is sexually possible for many men—and thus, couples—in later life, we also asked, (3) Does the magnitude of the observed associations differ before and after these drugs came on the market?     

Early changes in nutrient artery blood flow following tibial nailing with and without reaming: a preliminary study

OBJECTIVE: To quantify the changes in nutrient artery blood flow following reamed and unreamed nailing of intact canine tibias. DESIGN: In vivo animal study. INTERVENTION: Eighteen dogs underwent nutrient artery blood flow measurements over a fourteen-day period. The intervention groups consisted of controls (Group I), nailing without reaming (Group II), and nailing with reaming (Group III). MAIN OUTCOME MEASUREMENTS: Nutrient artery blood flow was measured through implantable ultrasonic blood flow probes placed around the nutrient artery of the tibia. RESULTS: Nutrient artery blood flow averaged 1.94 milliliters per minute over the fourteen-day period in Group I (no reaming or nailing performed). Nutrient artery blood flow following nailing without reaming (Group II) decreased to 44 percent of baseline values immediately after the procedure. By postoperative day 1, flow had decreased to 23 percent of baseline; over the fourteen-day period, nutrient artery blood flow recovered toward baseline values. Immediately following nailing with reaming (Group III), nutrient artery blood flow measured zero milliliters per minute. Over the fourteen-day period, nutrient artery blood flow in this group averaged 39 percent of the baseline level (range 19 to 58 percent). Whereas nutrient artery blood flow recovered toward baseline values (99 percent of baseline) by fourteen days in Group II, nutrient artery blood flow measured only 26 percent of the baseline level on postoperative day fourteen in Group III. CONCLUSIONS: The preliminary data suggest that nailing with reaming provides a double insult to the nutrient artery distribution.     

Simultaneous detection of BCL-2 protein, trisomy 12, retinoblastoma and P53 monoallelic gene deletions in B-cell chronic lymphocytic leukemia by fluorescence in situ hybridization (FISH): relation to disease status

Various genetic abnormalities are often found in B-CLL, but their relative importance in the pathogenesis and evolution of the disease has not been adequately clarified. We studied the expression of bcl-2 protein and the possible simultaneous occurrence of bcl-2 overexpression, trisomy 12 and the Rb1 and p53 gene deletions in 38 patients with B-CLL by combining immunophenotyping and dual color interphase FISH. We also looked for correlation between the genetic abnormalities and clinical parameters such as stage, disease duration from diagnosis to the time of study and overall survival. High expression of the bcl-2 protein was found in 76.3% of the patients (29/38). Trisomy 12 was found in 37% of cases (14/38) and Rb1 monoallelic gene deletion in 42% (16/38). The percentage of cells with hemizygous Rb1 deletion ranged from 13 to 18%. Monoallelic deletion of p53 was found in 29% of cases (11/38). The number of cells with only one signal ranged from 28 to 98%. Patients in stage A had on average, less than one abnormality, while patients in stage C had 2.6 abnormalities. Patients appeared to accumulate genetic abnormalities with time. Bcl-2 overexpression was found early in the course of the disease. Trisomy 12 appeared later, at about the same time as Rb1 deletion, but was not associated with adverse prognosis. Monoallelic deletion of p53 gene appeared rather late in the course of the disease and was associated with advanced stage. Despite the fact that more deaths occurred in the group of patients with three or four abnormalities and the presence of p53 gene deletion, differences in survival were not statistically significant, probably due to the limited number of patients in each group. A larger group of patients studied in a prospective manner will better clarify these issues in the future.     

Solitary bone metastasis beneath the shoulder shield: coincidence or cause?

Post-mastectomy radiotherapy has been demonstrated to improve locoregional control in breast cancer patients. We report a case involving a 44-year-old breast cancer patient who presented with a solitary bone metastasis in the area beneath the shoulder shield, likely from a coincidental recurrence.     

Nonfebrile Illness Seizures: A Unique Seizure Category?

PURPOSE: To describe the clinical characteristics of children with a first-time nonfebrile seizure in the setting of mild illness and to test the hypothesis that these seizures are associated with illness characterized by diarrhea. METHODS: This retrospective cohort study was performed in a pediatric emergency department. Patients ages 6 months to 6 years who were evaluated with first-time seizures were eligible for inclusion. Subjects were divided into three groups on the basis of symptoms accompanying their seizure: febrile (temperature, >38.0 degrees C with seizure), unprovoked (no symptoms of illness), and nonfebrile illness (no fever at the time of seizure, but other symptoms of illness present). RESULTS: Of the 323 children with first-time seizures, 247 (76%) had febrile seizure, 37 (12%) had unprovoked seizures, and 39 (12%) had nonfebrile illness seizures. Children with nonfebrile illness seizures were more likely than children with febrile seizures to have diarrheal illnesses accompanying their seizure (44 vs. 16%; p=0.001). Frequency of cough, rhinorrhea, and rash did not differ significantly between children with febrile and nonfebrile illness seizures. Diagnostic testing for infectious etiologies was not performed frequently in either group. CONCLUSIONS: Nonfebrile illness seizures may represent a distinct group of seizures with unique epidemiology. Further study to define this seizure group better is warranted.