Polymorphisms in the fetal progesterone receptor and a calcium-activated potassium channel isoform are associated with preterm birth in an Argentinian population.

OBJECTIVE: To investigate genetic etiologies of preterm birth (PTB) in Argentina through evaluation of single-nucleotide polymorphisms (SNPs) in candidate genes and population genetic admixture. STUDY DESIGN: Genotyping was performed in 389 families. Maternal, paternal and fetal effects were studied separately. Mitochondrial DNA (mtDNA) was sequenced in 50 males and 50 females. Y-chromosome anthropological markers were evaluated in 50 males. RESULT: Fetal association with PTB was found in the progesterone receptor (PGR, rs1942836; P=0.004). Maternal association with PTB was found in small conductance calcium activated potassium channel isoform 3 (KCNN3, rs883319; P=0.01). Gestational age associated with PTB in PGR rs1942836 at 32-36 weeks (P=0.0004). MtDNA sequencing determined 88 individuals had Amerindian consistent haplogroups. Two individuals had Amerindian Y-chromosome consistent haplotypes. CONCLUSION: This study replicates single locus fetal associations with PTB in PGR, maternal association in KCNN3, and demonstrates possible effects for divergent racial admixture on PTB.

Automated identification of neurons in 3D confocal datasets from zebrafish brainstem.

Many kinds of neuroscience data are being acquired regarding the dynamic behaviour and phenotypic diversity of nerve cells. But as the size, complexity and numbers of 3D neuroanatomical datasets grow ever larger, the need for automated detection and analysis of individual neurons takes on greater importance. We describe here a method that detects and identifies neurons within confocal image stacks acquired from the zebrafish brainstem. The first step is to create a template that incorporates the location of all known neurons within a population - in this case the population of reticulospinal cells. Once created, the template is used in conjunction with a sequence of algorithms to determine the 3D location and identity of all fluorescent neurons in each confocal dataset. After an image registration step, neurons are segmented within the confocal image stack and subsequently localized to specific locations within the brainstem template - in many instances identifying neurons as specific, individual reticulospinal cells. This image-processing sequence is fully automated except for the initial selection of three registration points on a maximum projection image. In analysing confocal image stacks that ranged considerably in image quality, we found that this method correctly identified on average approximately 80% of the neurons (if we assume that manual detection by experts constitutes 'ground truth'). Because this identification can be generated approximately 100 times faster than manual identification, it offers a considerable time savings for the investigation of zebrafish reticulospinal neurons. In addition to its cell identification function, this protocol might also be integrated with stereological techniques to enhance quantification of neurons in larger databases. Our focus has been on zebrafish brainstem systems, but the methods described should be applicable to diverse neural architectures including retina, hippocampus and cerebral cortex.

Insulin resistance in the HIV-infected population: the potential role of mitochondrial dysfunction.

Insulin resistance is accepted as the underlying fundamental defect that predates and ultimately leads to the development of type 2 (adult onset) diabetes mellitus in the general non-human immunodeficiency virus (HIV)-infected population. Insulin resistance is also a major component of the metabolic syndrome that, in association with other factors such as hypertension, hypercholesterolemia, and central obesity, defines a pre-diabetic atherogenic state that leads to adverse cardiovascular events. Growing evidence now suggests that mitochondrial dysfunction in skeletal muscle may be the mechanism whereby insulin resistance is induced. The prevalence of insulin resistance, glucose intolerance, and diabetes in the HIV-infected population has dramatically increased following the common use of highly active antiretroviral therapy (HAART). The development of insulin resistance in the HIV-infected population is likely to be multifactorial reflecting genetic predisposition, direct and indirect effects of both the protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor (NRTI) class of antiretroviral therapy, and a possible contribution from chronic inflammatory changes induced by HIV. Indirect effects of antiretroviral therapy on insulin resistance may be mediated through both the visceral adiposity and peripheral fat depletion components of lipodystrophy as well as through fatty infiltration in liver and muscle. Based on current knowledge, mitochondrial dysfunction can be hypothesized to play a key role in each of these components.

Extramammary metastatic neoplasms in the breast: a cytomorphological study of 11 cases.

The occurrence of metastatic tumours in the breast is uncommon and it is crucial for cytologists to be aware and distinguish them cytologically from primary breast tumours in fine needle aspirates. In the present retrospective study of 11 cases, over a 20-year period, we discuss the cytological features of extramammary metastatic tumours in the breast. A brief attempt has been made to discuss the past literature. The 11 metastatic tumours included four haematolymphoid neoplasms, two melanomas, two metastatic sarcomas and three metastatic carcinomas. A prior clinical diagnosis of the primary tumour was obtained in seven cases. Immunohistochemistry or histology following a cytological diagnosis confirmed all the cases. The main objective of this study was to highlight the use of cytology and at the same time caution the cytologist to be aware of the clinical/imaging findings and if necessary to utilize immunohistochemical facilities to consider/rule out the possibility of metastatic tumour in the breast.

Salmonella prosthetic joint septic arthritis.

We describe a case of Salmonella enteritidis infection of a prosthetic knee joint that was cured with ceftriaxone therapy for 6 weeks and replacement of the tibial component of the prosthesis. Eleven other cases of salmonella prosthetic joint infection have been reported in the English-language literature. Five infections occurred within 20 days of prosthesis placement, and seven occurred several months to years later; ten of 12 infections involved hip prostheses. Nine of 12 patients who had prosthesis removal were cured of the infection. Two of the three patients with retention of the prosthesis required long-term suppressive antibiotic therapy.

Relationship of extinction to perceptual thresholds for single stimuli.

OBJECTIVE: To demonstrate the effects of target stimulus intensity on extinction to double simultaneous stimuli. BACKGROUND: Attentional deficits contribute to extinction in patients with brain lesions, but extinction (i.e., masking) can also be produced in healthy subjects. The relationship of extinction to perceptual thresholds for single stimuli remains uncertain. METHODS: Brief electrical pulses were applied simultaneously to the left and right index fingers of 16 healthy volunteers (8 young and 8 elderly adults) and 4 patients with right brain stroke (RBS). The stimulus to be perceived (i.e., target stimulus) was given at the lowest perceptual threshold to perceive any single stimulus (i.e., Minimal) and at the threshold to perceive 100% of single stimuli. The mask stimulus (i.e., stimulus given to block the target) was applied to the contralateral hand at intensities just below discomfort. RESULTS: Extinction was less for target stimuli at 100% than Minimal threshold for healthy subjects. Extinction of left targets was greater in patients with RBS than elderly control subjects. Left targets were extinguished less than right in healthy subjects. In contrast, the majority of left targets were extinguished in patients with RBS even when right mask intensity was reduced below right 100% threshold for single stimuli. RBS patients had less extinction for right targets despite having greater left mask - threshold difference than control subjects. In patients with RBS, right "targets" at 100% threshold extinguished left "masks" (20%) almost as frequently as left masks extinguished right targets (32%). CONCLUSIONS: Subtle changes in target intensity affect extinction in healthy adults. Asymmetries in mask and target intensities (relative to single-stimulus perceptual thresholds) affect extinction in RBS patients less for left targets but more for right targets as compared with control subjects.

Train duration effects on perception: sensory deficit, neglect, and cerebral lateralization.

The mechanisms of conscious perception are uncertain. In a preliminary study, dramatic effects of train duration on perception in a patient with right brain stroke were noted. In this study, the mechanisms of train duration on perception of peripheral somatosensory stimuli are examined. Subjects included healthy adults and patients with right brain infarctions. Train duration effects on perception were examined in relation to cerebral infarction, handedness, age, elevated peripheral threshold via bupivacaine, and impaired attention via diazepam or scopolamine. Perceptual thresholds to electrical pulses on the hand decreased as train duration increased, but only over the first several hundred milliseconds. Compared to controls, right brain stroke patients showed much greater lowering of threshold in the affected hand as train duration was extended. Age and bupivacaine elevated thresholds, but had little or no influence on train duration effects. Diazepam and scopolamine had no effect on thresholds. Thresholds were lower in the left than right hand of healthy dextral subjects, irrespective of age. Sinistral subjects had less left/right asymmetry. Increased train duration effect in patients is not explained by a primary elevation in threshold or by impaired vigilance. Lower perceptual thresholds in the left hand of healthy dextral subjects is consistent with right cerebral dominance for externally directed attention.

Magnetic stimulation of visual cortex: factors influencing the perception of phosphenes.

Using transcranial magnetic stimulation of occipital cortex, the authors studied the stimulus parameters that generate phosphenes in healthy volunteers. Single pulses or trains of stimuli readily elicited phosphenes in all subjects. The threshold current needed to elicit perception of phosphenes was essentially the same for stimulus trains from 250 msec to 2000 msec in length, but increased dramatically for trains of shorter duration. The effect of stimulus frequency was variable, with each subject having a distinctive "frequency tuning curve," but overall, the threshold current necessary to produce phosphenes decreased as frequency of stimulation increased. Using paired pulses, the perceptual threshold was flat for interstimulus intervals between 2 msec and 100 msec, but increased rapidly as the interstimulus interval was increased above 100 msec. Stimulation of sites lateral to the midline elicited phosphenes in the contralateral visual field. Phosphenes were dominant in the lower and peripheral aspects of the visual fields. The findings are discussed in relation to similar studies of electrical stimulation of somatosensory cortex.

Blood products: optimal use, conservation, and safety.

A review of our experience in total joint arthroplasty revealed that the cell saver was not cost-effective in the case of routine primary hip or knee replacement. Its use should be restricted to cases of revision hip and knee surgery in which infection has been ruled out. Preoperative aspiration remains the most reliable method for accomplishing this. However, if the aspiration is negative and the intra-articular fluid obtained at the time of surgery is suspicious for infection, either in appearance or on Gram stain or cell count, it is best to abandon use of the cell saver. Predonation should be routine for all hip replacement cases unless there are specific contraindications. In general, there is good acceptance of this program by patients, although a few have specifically indicated they would prefer to run the risk of homologous transfusion. Two units available for primary replacement are more than ample. In cases of revisions, a first revision justifies a minimum of 3 units. For complex revision cases involving patients with three or more previous procedures on the hip, or those requiring significant bone resection or large segment grafting, the maximum possible number of units should be obtained. Autologous blood reinfusion should be done for essentially the same indications as homologous transfusion even though risks are sharply reduced. The local source for autologous collection will then follow its own specific protocol for the disposition of remaining units. In every case, the surgical technique should be careful and directed toward limiting intraoperative blood loss.

Subclavian vein thrombosis following fracture of the clavicle. A case report.

Clavicular fractures are common injuries, usually with uneventful sequela. A case of subclavian vein thrombosis following a clavicular shaft fracture is reported emphasizing the awareness and treatment of this uncommon complication.

The use of Ender's pins in extracapsular fractures of the hip.

In October 1976 a randomized, paired, prospective study comparing the compression sliding hip screw with Ender's pins in the treatment of extracapsular hip fractures was begun on the orthopaedic service at San Francisco General Hospital. The results in 100 patients with a minimum follow-up of six months showed that Ender's procedure required less operative time, had less blood loss, and had a lower postoperative incidence of medical complications. A 26 per cent incidence of technical problems with Ender's pins (such as postoperative backing-out of the pin) required reoperation in 16 per cent of the patients compared with an 8 per cent rate of reoperation in patients treated with the compression screw. The majority of these complications occurred in unstable fractures. There were no deep infections in the patients with Ender's pins but a 6 per cent incidence of deep infection was seen in those with the hip screws. There were no non-unions in either group. Although hip function at follow-up was equal in both groups, there was a 41 per cent incidence of postoperative pain and stiffness of the knee in the group with Ender's pins. It is our opinion that Ender's pins are a valuable addition to the armamentarium of surgeons treating extracapsular fractures of the hip and are ideally suited for elderly patients with stable fractures, particularly if the surgical risk is high. They must be used with caution in unstable fractures and postoperative protection in traction may be necessary. However, the occasional external rotation deformity and the high incidence of problems with the knee makes their use in younger, more active patients less desirable than the compression hip screw unless their unique advantages justify their use.

A multicenter study of the treatment of non-union with constant direct current.

A clinical study was initiated at the University of Pennsylvania in 1970 to evaluate the use of constant direct current in treating acquired non-union. In 1977 the study was expanded to include twelve participating investigators throughout the United States. The results indicate that, given proper electrical parameters and proper cast immobilization, a rate of bone union comparable to that seen with bone-graft surgery was achieved. Experience dictated that four cathodes, each delivering twenty microamperes of constant direct current for twelve weeks, were required to heal a non-union of a long bone. Of 178 non-union in 175 patients treated with adequate electricity in the University of Pennsylvania series, 149 (83.7 per cent) achieved solid bone union. Patients with a history of osteomyelitis had a healing rate of 74.4 per cent. The presence of previously inserted metallic fixation devices did not affect the end-result healing rate. Of eighty non-unions in seventy-nine patients treated with electricity in the participating investigators' series, fifty-eight (72.5 per cent) achieved solid bone union. Review of the non-unions treated unsuccessfully with constant direct current suggested that inadequate electricity, the presence of synovial pseudarthrosis or infection, and dislodgment of the electrodes are causes for failure with the procedure. Complications of the electrical treatment were minor and there was no deep infection resulting from this procedure in patients without previous osteomyelitis. We concluded that the practicing orthopaedic surgeon utilizing constant direct current to treat non-union should, by adhering to proper fracture management and by following the biophysical principles described herein, be able to achieve a rate of union comparable to that of bone-graft surgery, with a lower associated risk.

Acute coronary insufficiency. Review of 46 patients.

Forty-six patients admitted with acute coronary insufficiency are reviewed. All were investigated by coronary angiography; 4 had normal coronary arteries and are included in this study; the remainder had a distribution of coronary artery disease similar to other angina patients. The clinical and angiographic findings, management, and subsequent course of the other 42 patients are presented. Fourteen patients (33%) in whom rest pain persisted after 48 hours underwent emergency coronary angiography, with 3 deaths; of the surviving 11 who had acute saphenous vein bypass grafting, 2 died at operation and 3 had perioperative myocardial infarctions. Seventeen patients (41%) who initially improved required surgery within 6 months because of symptoms. Eleven patients (26%) were not operated on. It is concluded that acute coronary insufficiency is best managed initially by intensive medical therapy but a high proportion will require surgery later because of disabling angina. Early investigation and surgery are associated with a high mortality and incidence of myocardial infarction. Survivors of surgery are symptomatically improved and there is a low incidence of late infarction and death.

Left main stem coronary artery disease. Retrospective review of 26 patients treated surgically or medically.

The clinical, angiographic, exercise testing, operative, and follow-up data of 26 patients found at angiography to have left main stem coronary artery stenosis, defined as a reduction in the lumen diameter of 50% or more, are reviewed. There was a high incidence of significant proximal stenosis in the branches of the left main stem. No clinical features were found to distinguish patients with left main stem stenosis. All patients were considered for saphenous vein bypass grafting, selection being based upon the severity of symptoms, left ventricular function, and suitability of the coronary vessels for grafting. Two patients died within 24 hours of coronary angiography. Nine patients were operated on with no mortality. There has been one late cardiac death during a mean follow-up time of 13 months. All patients were symptomatically improved with a significant (P less than 0-01) increase in exercise ability postoperatively. Fifteen patients were not operated on. Six of these patients were regarded as operable but surgery was deferred; five have died at a mean time of 7-2 months. Five of the nine patients regarded as inoperable have died at a mean follow-up time of 14-8 months. The five non-surgical survivors remain symptomatic with no significant change in exercise ability. Recently reported surgical and medical series of patients with left main stem stenosis are reviewed.