Adrenarche in nonhuman primates: the evidence for it and the need to redefine it.

Adrenarche is most commonly defined as a prepubertal increase in circulating adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfo-conjugate (DHEAS). This event is thought to have evolved in humans and some great apes but not in Old World monkeys, perhaps to promote brain development. Whether adrenarche represents a shared, derived developmental event in humans and our closest relatives, adrenal androgen secretion (and its regulation) is of considerable clinical interest. Specifically, adrenal androgens play a significant role in the pathophysiology of polycystic ovarian disease and breast and prostate cancers. Understanding the development of androgen secretion by the human adrenal cortex and identifying a suitable model for its study are therefore of central importance for clinical and evolutionary concerns. This review will examine the evidence for adrenarche in nonhuman primates (NHP) and suggest that a broader definition of this developmental event is needed, including morphological, biochemical, and endocrine criteria. Using such a definition, evidence from recent studies suggests that adrenarche evolved in Old World primates but spans a relatively brief period early in development compared with humans and some great apes. This emphasizes the need for frequent longitudinal sampling in evaluating developmental changes in adrenal androgen secretion as well as the tenuous nature of existing evidence of adrenarche in some species among the great apes. Central to an understanding of the regulation of adrenal androgen production in humans is the recognition of the complex nature of adrenarche and the need for more carefully conducted comparative studies and a broader definition in order to promote investigation among NHP in particular.

Predicting age at onset of menopause: testing the "adaptive onset" hypothesis.

This study tests the "adaptive onset" hypothesis (AOH) proposed by Kuhle and explores the potential adaptive origins of menopause (Kuhle (2007) [3]). The AOH posits that both menopause and the timing of its onset are adaptive, and that age at onset may be mediated according to the likelihood of successful continued reproduction. Twelve factors were hypothesized to predict whether continued reproduction would be successful. Eight factors were tested using data extracted from the NLS Mature Women cohort. Statistical analyses reveal no support for predictions of the AOH; in fact, a majority of analyses suggest trends opposite from those predicted.

Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype.

OBJECTIVES: We aimed to examine the strength of association between traditional cardiovascular risk factors and carotid plaque development in systemic lupus erythematosus (SLE) patients and controls. We also aimed to determine which lupus-related factors are associated with carotid plaque and whether SLE sensitizes patients to the effects of traditional factors. METHODS: We studied 200 women with SLE and 100 controls. Demographic and risk factor data were collected and SLE features, including autoantibody profiles and therapy were noted. All subjects had B- mode ultrasound of their carotid arteries examined for the presence and distribution of plaque. RESULTS: SLE patients <55 years old had more plaque (21% vs 3% P < 0.01) and more SLE patients had plaque in the internal carotid artery (11% vs 4%; P < 0.05). Traditional risk factor models performed less well in SLE compared with controls [area under Receiver Operator Characteristic curves (AUC ROC) = 0.76 vs 0.90; P < 0.01]. A multivariable model using SLE factors only, performed significantly better (AUC ROC = 0.87; P < 0.01). The final model in SLE included age and cigarette pack-years smoking as well as azathioprine exposure ever, antiphospholipid antibodies (APLA) and previous arterial events (AUC ROC = 0.88). CONCLUSIONS: SLE patients have a higher prevalence and different distribution of carotid plaque than controls. SLE factors perform significantly better than traditional risk factors in their association with atherosclerosis in SLE and these factors add to the influence of traditional risk factors rather than sensitizing lupus patients to traditional factors. The SLE phenotype helps identify patients at increased risk of atherosclerosis.

Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome.

Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.

The March 2002 update of the electronic version of ICPC-2. A step forward to the use of ICD-10 as a nomenclature and a terminology for ICPC-2.

The electronic version of the second edition of the International Classification of Primary Care, ICPC-2-E, available on the website of Family Practice since 2000, needed an update of the mapping with ICD-10 as a nomenclature and, consequently, of some of its criteria. This is now being made available, together with the full four-digit conversion structure between the two systems, in an electronic form, allowing the use of the alphabetical index of ICD-10 in several languages to be used as a terminology for ICPC-2. In this contribution, we discuss the considerations for preparing this new mapping structure, and its potential use in future electronic patient records in family practice.

Rod diameter prediction in patients with osteogenesis imperfecta undergoing primary osteotomy.

SUMMARY: Because the cross-sectional shape of the long bones of patients with osteogenesis imperfecta is often elliptical, the use of preoperative radiographs to determine intramedullary rod diameter in these patients undergoing osteotomy may be misleading. To investigate this, the authors correlated the narrowest inner bone diameter (NID) on preoperative radiographs to the rod diameter (RD) on postoperative radiographs. The authors evaluated 79 bones in 27 patients undergoing primary osteotomy with intramedullary fixation. Only 5% of the bones had an equal NID and RD, with 81% of bones having a smaller RD than the measured NID. Although a positive correlation was found between RD and NID (correlation coefficient 0.76), measurement of the NID on preoperative radiographs did not provide a good prediction of the actual RD used in this series of children with osteogenesis imperfecta.

Use of an automated device for alternative site blood glucose monitoring.

OBJECTIVE: To evaluate the accuracy, comfort, and ease of use of a new automated device for blood glucose monitoring using the arm as an alternative sampling site. RESEARCH DESIGN AND METHODS: These studies use an automated hand-held device that applies a small vacuum, lances the skin, transfers blood onto an electrochemical test strip, and measures glucose. Patients who had type 1 or type 2 diabetes and had received no prior training using this device were recruited from five diabetes clinics. Testing was performed by the patients using this device and by trained healthcare professionals. Blood glucose was measured by 354 patients: from the arm using the device, from the finger using a laboratory reference instrument, and from the finger using the device via the secondary test port. Each patient completed a questionnaire rating the level of pain and ease of use of the device. RESULTS: Blood glucose results in samples obtained from the arm with the automated device agreed well with finger-stick plasma glucose results using a reference instrument (regression slope 0.98, intercept 0.01 mmol/l [0.1 mg/dl], r = 0.96). Error grid analysis showed that 100% of the measurements fell within zones A and B. In the survey, 60% of the patients reported that arm testing with the automated device was "painless;" another 31% of the patients stated that it was "much less painful," and 6% of patients considered using the device "less painful" than finger-stick testing. In a survey containing 15 questions for rating the ease of use with a scale of 1 to 6, the overall mean rating was 5.5. CONCLUSIONS: The automated device is easy to use and provides accurate glucose results; 97% of the patients found it less painful than finger-stick testing.

A new suture for hair transplantation: poliglecaprone 25.

BACKGROUND: The most common type of donor closure in hair transplantation is with nonabsorbable, running sutures, usually of nylon or polypropylene. This is accomplished with or without buried absorbable sutures. Another popular method of closure is with stainless steel staples. Each of these methods has benefits and limitations with respect to healing, comfort, and convenience for the patient. OBJECTIVE: The purpose of this study is to describe the use of poliglecaprone 25, a synthetic, absorbable, monofilament suture in hair transplantation surgery, to detail the suturing techniques needed to maximize the benefit of this suture, and to compare this material and suturing technique to a well-established form of closure, that of metal staples in a bilaterally controlled fashion. METHODS: Poliglecaprone 25 is a synthetic, absorbable monofilament suture of low tissue reactivity. It was compared to closure with metal staples in a bilateral controlled study. One side of the donor area was closed with poliglecaprone 25 sutures using a running cutaneous stitch and the other side was closed with stainless steel staples. Patients were evaluated with regard to healing, postoperative discomfort, resultant surgical scar, and closure material preference. RESULTS: Of the 22 patients studied, the following postoperative complaints were noted on the staples side: tenderness (12), itching (4), swelling (2), and scabbing (1). This compared to only one complaint of itching and one complaint of swelling on the poliglecaprone 25 side. Two patients had postoperative complaints of visibility of staples showing through their hair. Objective measurements revealed a wider scar overall on the staples side in six patients and wider scar on the suture side in two patients. The average scar width on the staples side measured 1.78 mm compared to 1.42 mm on the suture side. Fourteen of the 22 patients preferred poliglecaprone 25 for future procedures, 1 preferred metal staples, and 7 had no preference. Most patients stated that postoperative discomfort from the staples and the inconvenience and occasional pain associated with their removal was responsible for their decision. CONCLUSION: Poliglecaprone 25 is a strong synthetic, absorbable, monofilament suture with low tissue reactivity that can be used in hair transplantation to close the donor wound with a single, running cutaneous stitch. This suture can provide a donor closure that ensures hemostasis, has little risk of infection, and is comfortable for the patient. If specific surgical techniques are followed, this suture can provide a donor closure that ensures hemostasis has little risk of complications, is both comfortable and convenient for the patient postoperatively and results in a fine surgical scar.

Injections and surgical therapy in chronic pain.

OBJECTIVE: The purpose of this review was to determine how effective surgery and injection therapy are in the management of chronic pain. METHODOLOGY: A standardized literature search identified seven systematic reviews of the literature and six randomized controlled trials to provide evidence about surgery and injection therapy for chronic pain. RESULTS: Some study subjects had highly specific diagnoses, whereas other study subject groups had nonspecific pain, including multiple conditions. The timing of treatment interventions was generally unclear, and few studies analyzed subgroups. Overall, there was a lack of methodologically sound studies of surgery and injection therapies. CONCLUSIONS: Standard discectomy compared with conservative treatment for proven disc herniation (< or = 1 year) and local triamcinolone injection for lateral epicondylitis (< or = 12 weeks) are both effective for pain relief (level 2). There was limited evidence of effectiveness (level 3) of intraoperative steroid at discectomy, epidural steroid injection for sciatica with low back pain, caudal steroid injection for low back pain, local glycosaminoglycan polyphosphate injection for lateral epicondylitis, intraarticular steroid injection for shoulder arthritis, subacromial steroid injections for rotator cuff tendinitis, nonspecific injections for painful shoulder, systemic growth hormone for fibromyalgia, and intravenous adenosine for fibromyalgia. There was limited evidence (level 3) that there is no additional benefit of adding steroid to local anesthetic in caudal epidural injections. There is limited evidence (level 3) that intravenous adenosine is ineffective for fibromyalgia. The remaining evidence was inadequate (level 4a) or contradictory (level 4b).

Nonunion of a Hoffa fracture in a child.

The authors report a case of a Hoffa fracture of the lateral femoral condyle that subsequently went on to nonunion in an eight-year-old child. The child presented with symptoms of knee pain and snapping five years after a motor vehicle accident. The nonunion fragment involved most of the lateral femoral condylar articular surface but spared the physis. After treatment by open reduction and limited internal fixation, the nonunion has healed, and the child has virtually full range of motion of the knee and no evidence of growth disturbance.

Regulation of germline promoters by the two human Ig heavy chain 3' alpha enhancers.

The human IgH 3' enhancers, located downstream of each of the two Calpha genes, modulate germline (GL) transcription of the IgH genes by influencing the activity of promoter-enhancer complexes upstream of the switch and intervening (I) regions. The regulation of GL alpha1 and alpha2 promoters by different human 3' enhancer fragments was investigated in cell lines representing various developmental stages. Both alpha1HS1,2 and alpha2HS1,2 fragments show equally strong enhancer activity on the GL alpha1 and alpha2 promoters in both orientations when transiently transfected into a number of mature B cell line (DG75, CL-01, and HS Sultan). However, there is no activity in a human pre-B cell line (NALM-6) nor a human T cell line (Jurkat). HS3 shows no enhancer activity by itself in any of the cell lines, whereas a modest effect is noted using HS4 in the three mature B cell lines. However, the combination of the alpha2HS3-HS1,2-HS4 fragments, which together form a potential locus control region, displays a markedly stronger enhancer activity than the individual fragments with a differential effect on the alpha1 and alpha2 promoters as compared with the gamma3 promoter. Our results suggest that the human GL alpha promoter may be regulated by two independent pathways. One pathway is induced by TGF-beta1 which directs IgA isotype switch through activation of the GL alpha promoter and no TGF-beta1-responsive elements are present in the different 3' enhancer fragments. The other route is through the human 3' enhancer regions that cis-up-regulate the GL alpha promoter activity in mature B cells.

The logic of follicular unit transplantation.

Follicular unit transplantation is a method of hair restoration surgery where hair is transplanted exclusively in its naturally occurring, individual follicular units. The evolution and rational for follicular unit transplantation will be discussed, as well as the logic for the various techniques used in its implementation. Specifically, the logic for single strip harvesting, stereo-microscopic dissection, automated graft insertion, and large transplant sessions will be reviewed. The central role of the follicular unit constant in the surgical planning will also be discussed.

Construction and binding analysis of recombinant single-chain TCR derived from tumor-infiltrating lymphocytes and a cytotoxic T lymphocyte clone directed against MAGE-1.

The TCR is responsible for the specificity of cytotoxic T lymphocytes (CTL) by recognizing peptides presented in the context of MHC. By producing recombinant soluble TCR, it is possible to study this interaction at the molecular level. We generated single-chain TCR (scTCR) from tumor infiltrating lymphocytes (TIL) and one CTL clone directed against melanoma-associated antigen (MAGE)-1. Sixty-eight day anti-MAGE-1 TIL and one cloned anti-MAGE-1 CTL were analyzed by PCR for their Valpha and Vbeta gene usage. The TIL population showed a restriction in Valpha and Vbeta usage with only Valpha4 and Valpha9 and Vbeta2 and Vbeta7 expressed. The anti-MAGE-1 CTL clone demonstrated absolute restriction with only Valpha12 and Vbeta1 expressed. DNA sequence analysis was performed on all V regions. For the TIL, each possible Valpha-Vbeta combination (i.e. Valpha4-Vbeta2, Valpha9-Vbeta2, Valpha4-Vbeta7 and Valpha9-Vbeta7) was constructed as a distinct scTCR and the recombinant proteins expressed in bacteria. From the anti-MAGE-1 TIL, Valpha4-Vbeta2 scTCR demonstrated binding activity to HLA-A1(+) cells pulsed with MAGE-1 peptide. Results obtained from screening a panel of our scTCR constructs on HLA-A1(+) cells pulsed with MAGE-1 peptide or irrelevant peptide demonstrated that Vbeta2 plays a significant role in binding to the MAGE-1 peptide. Amino acid alignment analysis showed that each Vbeta sequence is distinctly different from the others. These findings demonstrate that soluble TCR in single-chain format have binding activity. Furthermore, the results indicate that in TCR, like antibodies, one chain may contribute a dominant portion of the binding activity.

Drugs and toxins: fact and fancy.

The scientific approach has reduced the burden of disease in society and removed much of the mystery, yet there is still much subjective illness and unease. Fear of poisoned water, bad food, and bad air may have been of evolutionary advantage to early humans, and these fears remain potent in today's sophisticated world. Perhaps the twenty-first century will see an understanding at the molecular and genetic level of the mechanisms underlying belief and its consequences.

Standardizing the classification and description of follicular unit transplantation and mini-micrografting techniques. The American Society for Dermatologic Surgery, Inc.

Previous attempts at classifying small graft transplants have focused mainly upon graft size and have not taken into consideration other technical factors involved in graft production that may influence the outcome of the surgery. The proposed classification attempts to consider these factors by including various technical aspects of harvesting, dissection, and placement, all of which impact the quality and quantity of the small grafts used in the procedure. By standardizing the nomenclature, as well as the description of the other factors involved in the surgery, communication between physicians and patients may be facilitated. In addition, different procedures may be more accurately studied and compared.

Dissecting microscope versus magnifying loupes with transillumination in the preparation of follicular unit grafts. A bilateral controlled study.

BACKGROUND: The increasing importance that hair transplant surgeons are placing on maintaining the integrity of the naturally occurring follicular unit has generated great interest in finding the ideal method of graft dissection. OBJECTIVE: The present study attempts to compare two popular dissecting techniques: the dissecting microscope, and magnifying loupes with transillumination, in the preparation of follicular unit grafts. METHODS: Donor strips from 41 patients were used in a prospective, bilateral controlled fashion to compare the two different dissecting techniques. RESULTS: Microscopic dissection produced a 17% greater yield of hair as compared with magnifying loupes with transillumination. CONCLUSION: The results of this study show an increase in the yield of follicular unit grafts, as well as the total amount of hair harvested from the donor strip, when using the dissecting microscope as compared with magnifying loupes with transillumination. This increase was observed when only the latter part of the dissecting procedure was studied. When complete microscopic dissection is used, the advantage should be even more significant.

Rapid Fire Hair Implanter Carousel. A new surgical instrument for the automation of hair transplantation.

BACKGROUND: As hair transplantation evolved into a procedure in which large numbers of very small grafts are moved in a single session, new problems have emerged. These include greater staffing requirements, longer operating time, additional technical difficulties, and increasing problems with quality control. OBJECTIVE: To introduce a new surgical instrument, the Rapid Fire Hair Implanter Carousel (Carousel), which can automate the most labor-intensive parts of the hair transplantation process, site creation and implant placement, by combining them into a single step and delivering them in rapid sequence. This instrumentation should help to minimize some of the human factors contributing to graft injury and to simplify and increase the speed of the hair transplant procedure. METHODS: In a patient with a Norwood IIIA balding pattern, 400 follicular implants were placed into a specific section of the bald scalp. The remainder of the bald scalp was transplanted with 800 follicular implants placed in the traditional way. The two areas were monitored and compared for intraoperative bleeding, ease of placing, total placing time, postoperative healing, and hair growth. Photographic documentation was obtained after surgery and at each postoperative visit. RESULTS: The Carousel visually produced less bleeding when compared with the manual approach. The Carousel was easier to use than the manual technique, since it eliminated graft insertion as a separate step. This was evidenced by the significantly shorter time required to insert the implants (40 grafts/minute with the Carousel vs 6.6 grafts/minute manually) and the decreased need for secondary manipulation once the grafts were inserted. Postoperative healing of the two groups were the same with regard to the duration of crusting and erythema. The rate of hair growth and the total amount of hair observed at 4 months were the same when identical size areas in test and control sides were compared. CONCLUSION: In this single patient pilot study, the Carousel greatly facilitated the placement of grafts by decreasing bleeding and obviating the extra step needed for the insertion of the implants. As a result, the total operative time decreased, shortening the time the grafts were outside the body, and decreasing the risk of desiccation and warming. By minimizing the human factor in this labor-intensive part of the procedure, the quality of the hair transplant should increase. It is anticipated that these benefits will result in increased hair yield. Further studies are needed, in a larger patient group, so that these benefits can be demonstrated.