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Tacrolimus-induced cardiomyopathy (TICM) is a rare but serious adverse effect of tacrolimus, which has been described primarily in pediatric non-renal transplant recipients. We describe a case of TICM in an adult renal transplant recipient that resulted in allograft dysfunction and multiple hospital admissions for heart failure exacerbation. Prompt and complete reversal of TICM occurred after tacrolimus discontinuation. Although tacrolimus-induced cardiomyopathy is reversible, availability of alternative immunosuppressants is limited, particularly in the setting of renal dysfunction. Available studies and patient-specific factors must be considered when determining an alternative maintenance immunosuppression regimen. We chose to use belatacept as alternative immunosuppression in this patient with TICM. Over the next 3 years, the patient remained free of hospital admissions and acute rejection, and demonstrated superior renal allograft function than was observed before her first heart failure admission. We believe that belatacept is an acceptable alternative to tacrolimus therapy for resolution of TICM., (© 2015 Pharmacotherapy Publications, Inc.)

Objectives: The authors explored consistency of the observed running order in operating sequence compared with prior scheduled listing. We analysed potential variables felt to be predictive in the chances of a patient having their procedure as previously scheduled., Methods: Data were retrospectively collected for a consecutive group of patients who underwent elective maxillofacial procedures over a four week period. The consistency of scheduled and observed running order was documented. We considered four independent variables (original list position, day of week, morning or afternoon list, seniority of surgeon) and analysed their relationship to the probability of a patient undergoing their operation as per listing. Logistic regression analysis was used to determine significant associations between predictor variables with an altered list order., Results: Data were available for 35 lists (n = 133). 49% of lists were found to run according to prior given order, the remainder subject to some alteration. Logistic regression analysis showed a statistically significant association between original scheduled position and day of week, with list position consistency. Patients listed first were twelve times more likely to have their operation as listed compared to those placed fourth (OR 12.7, 95% CI 3.7-43, p < 0.05). Operating lists at the start of a week were subject to less alteration (p < 0.05). There was no demonstrated relationship between the grade of surgeon operating and alteration in operating sequence., Conclusion: Approximately half of lists showed some alteration to the previously printed order. It appears that being first on an elective list offers the greatest guarantee that a patient will have their operation as per prior schedule. It may be reasonable for clinicians to be mindful of potential operating list alterations when preparing their patients for elective surgery., (Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Purpose: Vascular access has been described in the literature anywhere from the 'Achilles Heel' to the 'Cornerstone' of haemodialysis. Displacement of a central venous catheter is not an uncommon occurrence. We discuss an alternative method of placement for the tunnelled central venous catheter to prevent displacement in those patients with excess anterior chest wall soft tissue., Methods: A new surgical technique for placement of a tunnelled central venous catheter was developed in an attempt to reduce the number of displacements. This involved the creation of a second tunnel at a 90° angle to the original retrograde tunnelled path., Results: The authors have currently placed five 'S-Line' tunnelled central venous catheters with no reports of displacement or line infection over a period of 18 months., Conclusions: The 'S-Line' offers a simple, straightforward and most importantly safe method to reduce the incidence of tunnelled right internal jugular central venous catheter displacement.

Background: Recurrent focal segmental glomerular sclerosis (rFSGS) in renal transplant recipients (RTR) is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies., Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure, requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb), soluble urokinase-type plasminogen activator receptor (suPAR) serum level with suPAR-β3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab) titer., Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, β3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance), and high dose steroids, the Palb and suPAR-β3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation, we commenced adrenocorticotropic hormone (ACTH, Acthar(®) Gel), 80 units subcutaneously twice weekly. Four-weeks later, he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with <1 g of proteinuria., Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.

Recurrent epistaxis is very common in children, and the majority of cases are self-limiting with simple first aid measures. However, recurrent episodes are a source of distress and anxiety for child and parent alike, and commonly result in hospital referral. We present a structured approach highlighting initial assessment, examination and management including when to refer to ear, nose and throat (ENT) surgery., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We explored how oral and maxillofacial (OMF) consultants describe themselves in their correspondence. We did a telephone survey of OMF surgeons' secretaries and compiled data on the specialist titles used. Data were available for 290 consultants and 19 different titles were identified. A total of 190 (66%) consultants used the title OMF surgeon alone and a further 22 (8%) combined it with the name of a subspecialty. The remaining 78 (27%) used 11 alternative titles. Of those surveyed, 212 (73%) continue to use the specialty title of OMF surgeon with or without the name of a subspecialty comprising a readily identifiable group of specialists., (Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study is to determine the clinicopathological features of breast cancer in two dedicated cancer treatment centers in north Trinidad. The histological types and stage at presentation were also investigated., Design and Methods: A retrospective cohort design was used; data were collected from a review of medical records of patients meeting the entry criteria. Clinical and demographic data were extracted., Results: A total of 640 patients were selected for the study and were available for the analysis. The annual cumulative incidence rate of breast cancer for the calendar years 2010 and 2011 in north Trinidad was 32.4 per 100,000 and 24.6 per 100,000 of the population. The age group between 51-60 years had the highest proportion of cases of breast cancer. There was a significant ethnic disparity in the occurrence of breast cancer, as it was more common in people of African origin than among South East Asians. Surgery and chemotherapy were the major interventions employed., Conclusion: Breast cancer prevalence continues to be high in Trinidad; we provide evidence of the extent of and the degree of sophistication required to care for patients with breast cancer in a health care system in a small developing country.

Hyperammonemia, post-orthotopic lung transplantation, is a rare but mostly fatal complication. Various therapies, including those to decrease ammonia generation, increase nitrogen excretion, and several dialytic methods for removing ammonia have been tried. We describe three lung transplant recipients who developed acute hyperammonemia early after transplantation. Two of the three patients survived after a multidisciplinary approach including discontinuation of drugs, which impair urea cycle, aggressive ammonia reduction with prolonged daily intermittent hemodialysis (HD), and overnight slow low-efficiency dialysis in conjunction with early weaning of steroids and other therapeutic measures. Our experience suggests that early initiation of dialysis, high dialysis dose, increased frequency, and HD preferably to less efficient modalities increases survival in these patients., (© 2013 International Society for Hemodialysis.)

Bjørnstad syndrome is an extremely rare condition characterized by pilitorti and nerve deafness. Only few large families have been reported worldwide. Here we describe a large Pakistani family with five affected individuals. The hair fibers of all the patients were twisted around their axis and devoid of any pigment. In addition the patients had a moderate-to-severe degree of hearing impairment. Genotyping with high-density single-nucleotide polymorphism arrays showed homozygosity in two intervals on chromosome 2. Linkage with one of these regions (genomic position 218745685-221025443, hg19) was confirmed. This region encompasses the BCS1L gene. Mutations in this gene have previously been associated with Bjørnstad's syndrome. We sequenced the BCS1L gene for identification of the causative mutation in the family. A novel homozygous missense mutation c.901T>A was identified, which segregated with the disease in the family. This mutation results in the amino acid change p.Tyr301Asn and was predicted to be pathogenic by bioinformatics tools.

We report a case of severe systemic loxoscelism in a previously healthy young man. This was associated with a Coombs-positive hemolytic anemia, striking leukomid reaction, renal failure, respiratory failure and cardiovascular collapse. This is the first documented case of a renal biopsy in a patient with renal failure after envenomation by the brown recluse spider. Associated systemic toxicity usually resolves but requires prompt recognition and supportive care in an intensive care setting. We also discuss the potential mechanism by which the venom of this small spider can lead to multiorgan failure and possibly death.

Patients with myeloproliferative disorders (MPDs), such as essential thrombocythemia (ET) have increased risk of thrombosis and bleeding, which are major sources of morbidity and mortality. Most MPD patients have a gain of function mutation in Janus kinase 2 (JAK2V617F), but little is known how JAK2V617F affects platelet function. Here, we demonstrate that platelets from ET patients have impaired SFLLRN-mediated fibrinogen binding and have lost the potentiating effect of thrombopoietin (which couples to JAK2) on this pathway. In contrast, SFLLRN-mediated P-selectin expression, ATP secretion, phosphorylation of the PKC substrate pleckstrin, and Ca(2+) mobilization were unaffected in JAK2V617F positive platelets. In addition, thrombopoietin-mediated JAK2 phosphorylation was unchanged, suggesting that signaling pathways activated downstream of JAK2 are impaired. Indeed, we found that platelets from JAK2V617F positive ET patients have significantly reduced phosphorylation of the PI3 kinase substrate Akt, and have reduced activation of Rap1 in response to thrombopoietin, IGF-1,ADP, SFLLRN, and thrombin. This effect was independent of Giα P2Y12 purinergic receptor function as ADP-mediated inhibition of VASP phosphorylation was unchanged. These results demonstrate that the PI3 kinase/Rap1 pathway is intrinsically impaired in platelets from JAK2V617F-positive ET patients, resulting in diminished thrombin and thrombopoietin-mediated integrin α(IIb)β(3) activation.

A series of N,N',N''-trisubstituted guanidines (1-6) and their copper(II) complexes, [κ(2)(O,N)-C(6)H(5)CONHC(NHC(6)H(4)Cl)NR](2)Cu(ii) (R = iso-propyl (1a), n-butyl (2a), sec-butyl (3a), tert-butyl (4a), benzyl (5a), and para-tolyl (6a)) were synthesized and characterized using elemental analysis, FTIR and NMR spectroscopy. DFT studies were used to assess the location of the protons in the free ligands. However, calculations have shown that, in all cases, hydrogen bonding from either N-H group gives conformations that are very similar in energy. Single crystal XRD studies were used to characterize ligands 1 and 4 and the related complexes 1a and 4a. The structures reveal that these complexes are mononuclear in the solid state and that copper adopts a regular square planar geometry. In both metallic species, the N, N', N''-trisubstituted guanidine ligands chelate the Cu(II) atom using the oxygen and one nitrogen. The synthesized compounds were investigated for urease inhibition using thiourea as a standard drug. Most complexes exhibit a better activity than the respective guanidines and compound 1a was found to be the most active with IC(50) = 9.83 ± 0.07 μM (the IC(50) for thiourea is 21.0 ± 0.1 μM). The species were also screened for their anti-leishmanial activity. However, all of the compounds were devoid of any significant activity., (This journal is © The Royal Society of Chemistry 2011)

Background: Previous small studies suggested SBOT may be ineffective in relieving breathlessness after exercise in COPD., Methods: 34 COPD patients with FEV1 <40% predicted and resting oxygen saturation ≥93% undertook an exercise step test 4 times. After exercise, patients were given 4 l/min of oxygen from a simple face mask, 4 l/min air from a face mask (single blind), air from a fan or no intervention., Results: Average oxygen saturation fell from 95.0% to 91.3% after exercise. The mean time to subjective recovery was 3.3 minutes with no difference between treatments. The mean Borg breathlessness score was 1.5/10 at rest, rising to 5.1/10 at the end of exercise (No breathlessness = 0, worst possible breathlessness = 10). Oxygen therapy had no discernable effect on Borg scores even for 14 patients who desaturated below 90%. 15 patients had no preferred treatment, 7 preferred oxygen, 6 preferred the fan, 3 preferred air via a mask and 3 preferred room air., Conclusions: This study provides no support for the idea that COPD patients who are not hypoxaemic at rest derive noticeable benefit from oxygen therapy after exercise. Use of air from a mask or from a fan had no apparent physiological or placebo effect.

Fractions obtained from partitioning of aerial methanolic extract of Euphorbia Aelleniiwith chloroform (E2), ethyl acetate (E3), n-butanol (E4) and water (E5) were investigated in vitro for their phytotoxicity, insecticidal, anti-leishmanial, cytotoxicity, antibacterial and antifungal activities. Sample E2 appeared to have significant phytotoxic activity. In the insecticidal screening study only one of the insects, Rhyzopertha dominica, showed acceptable mortality after treatment with E2, but weak response to E3 and E4 fractions. Leishmanicidal activity of the chloroform fraction was present, but not very significant. E2 showed favorable cytotoxic activity, while E3 had weak activity, and the other samples had no significant activity. In the antifungal screening tests; E2, E3 and E4 fractions exhibited about 25% inhibition of fungal growth against Fusariumsolani, while they were not active against other tested fungi. The results of antibacterial screening were completely negative, which may be due to resistance towards these types of constituents.

Haematopoietic stem cell transplantation (HSCT) is widely used to treat patients with a range of haematological and non-haematological disorders. Both bone marrow and peripheral blood stem cell collection are associated with morbidity and, very rarely, mortality. We investigated the information that exists to adequately inform donors about the relative merits of each procedure. We carried out a systematic review analysing data from six prospective randomised controlled trials of related donors and discuss here the merits and drawbacks of this approach. Registry data mostly describes patient outcome but stem cell donor registries collect and report information on unrelated donors which could easily be extended to related donors. Further well-designed, randomised studies are required.

Background: Haemopoietic stem cells can be collected from a donor either as a bone marrow harvest or by peripheral blood collection. Both techniques have risks for the donor., Objectives: The aim of this review was to identify the adverse effects of haemopoietic stem cell donation and to compare the tolerability and safety of the two methods., Search Strategy: We searched bibliographic databases including the Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library 2008, issue 2), MEDLINE and EMBASE up to May 2008. We also searched reference lists of articles and contacted experts in the field., Selection Criteria: Randomised controlled trials enrolling haemopoietic stem cell donors and evaluating the different methods of donating haemopoietic stem cells were eligible., Data Collection and Analysis: Two authors independently screened studies for inclusion. We extracted data and evaluated methodological quality. Quantitative analysis was not possible for most outcomes, but where used we preferred random-effects models due to the variability between the included studies., Main Results: Six trials (807 donors) were eligible: all were substudies, or constituent parts of, larger randomised controlled trials of bone marrow and peripheral blood stem cell allogeneic transplantation. No included trial was designed solely to measure and assess the experience of stem cell donors. The donors in all studies were related to the stem cell recipient. Overall, both types of donors experienced pain subsequent to donation, and psychological morbidity. The trend was for bone marrow donors to experience more pain at the donation site, more overall adverse events, and more days of restricted activity. They were also more likely to require hospitalisation than peripheral blood stem cell donors. In contrast, peripheral blood stem cell donors experienced more pain prior to donation, which may be related to the pre-donation administration of granulocyte colony stimulating factor (G-CSF). The methodological quality of the studies was poor and indicated limitations due to the risk of selection and attrition bias. The proportion of donors from the parent trial not included in the donor substudies was also inadequately explained., Authors' Conclusions: The different short-term morbidities associated with each type of haemopoietic stem cell donation were clear, with bone marrow donors experiencing more pain and more restriction post-donation than peripheral blood donors. However, the studies were limited by their methodological quality, failure to provide long-term follow up (for which larger numbers of donors would be required) and a failure to apply consistent measures of quality of life in a way which allows more meaningful evaluation across studies.

Objective: To compare clinical presentation of benign and malignant ovarian tumours and to enlist and identify symptoms that could lead to early diagnosis of ovarian carcinoma, Methods: It was a consecutive case series study. All patients who on abdominal or bimanual examination and abdominal U/S were found to have ovarian cyst or tumour, and later underwent laparotomy were included., Results: The study included 110 patients, of whom 80 (72%) had benign and the rest malignant disease. Mean age of patients with malignancy was 49.07+/-18.5 years and for benign 36.95+/-8.2 years (p= 0.0001). Eleven patients with benign tumours were asymptomatic, while 66% had abdominal pain. On the other hand 70% patients with ovarian malignancy had abdominal symptoms with abdominal pain in (76%). Abdominal enlargement and abdominal mass were significantly more in malignant tumours (p=0.003, p= 0.005). Gastrointestinal symptoms were present in both groups but more significant in malignant group (p=0.004). Constitutional symptoms like loss of appetite and weight loss were only present in malignant group (p=0.001). Seventy percent of the malignant tumours presented at late stage (III & IV). Histopathology of benign tumours revealed follicular/luteal cyst in 32% cases while serous cyst adenoma in 23%. Histopathology of malignant tumours showed serous cyst carcinoma in 46.7% and mucinous cyst carcinoma in 26% cases., Conclusions: Ovarian malignancy is a silent killer, especially affecting women above 50 years. Although presentation is often vague and non specific, symptoms are definitely present. Therefore a proper bimanual examination and appropriate investigations should be done at the outset in post menopausal women.

Introduction: To study the prevalence of cardiac disease in pregnancy and to assess the foetomaternal outcomes., Methods: It was a 5 year descriptive study. All pregnant females with a known or newly diagnosed congenital or acquired cardiac lesion on echo cardiography were included in the study., Results: There were 17,056 births during the study period, of whom 160 were cardiac patients giving a prevalence of 1%. Out of these 36% patients were diagnosed to have cardiac disease during current pregnancy. Acquired valvular heart lesions were found in 132 (82%) patients with mitral stenosis being the commonest (55%), others were congenital. Of the group, 43% patients were in class III & IV according to NYHA. Majority delivered vaginally and only 29% had c/section, 9% had therapeutic termination of pregnancy and 45% babies were low birth weight. Ten babies expired. Maternal mortality was low (3.8%), while 55(35%) had obstetric complications. Poor functional class (III & IV) was the key determinant of adverse footomaternal outcome (p<0.0001)., Conclusion: The good results of this study can be attrihuted to the team efforts of between obstetricians, cardiologists and patients. Adverse foetomaternal outcome was related to poor functional class III and IV of NYHA.

We report a case of 54-year-old man who presented to hospital with severe prolonged retrosternal chest pain of anginal nature. Electrocardiogram taken by his general practitioner showed minimal ST elevation in chest leads V1 and V2; there was also marked right axis deviation of P wave (negative in lead I and aVL) and of QRS complexes, together with low voltage in precordial leads V4 through V6 suggestive of dextrocardia. Repeat electrocardiogram with chest and limb leads reversed showed widespread, significant ST elevation in lead I, aVL, and V1 through V5 in keeping with extensive acute anterior myocardial infarction (MI). High cardiac enzymes and troponin level provided further confirmation. The extent of MI in such patients may be underestimated unless dextrocardia is timely recognized and leads reversed. We recommend that for patients with dextrocardia and situs inversus presenting with MI, both chest and limb leads be reversed to reveal the true extent of the infracted area.

Objective: Although there have been case reports suggesting a relationship between treatment with the acne medication isotretinoin and the development of depression and suicide, this topic remains controversial. In order for isotretinoin to cause depression, it must have an effect on the brain; however, the effects of isotretinoin on brain functioning in acne patients have not been established. The purpose of this study was to assess the effects of isotretinoin on brain functioning in acne patients., Method: Brain functioning in adults was measured with [(18)F]fluorodeoxyglucose positron emission tomography before and after 4 months of treatment with isotretinoin (N=13) or an antibiotic (N=15)., Results: Isotretinoin but not antibiotic treatment was associated with decreased brain metabolism in the orbitofrontal cortex (-21% change versus 2% change for antibiotic), a brain area known to mediate symptoms of depression. There were no differences in the severity of depressive symptoms between the isotretinoin and antibiotic treatment groups before or after treatment., Conclusions: This study suggests that isotretinoin treatment is associated with changes in brain functioning.

Phenytoin (Dilantin) is an anticonvulsant used in the treatment of epilepsy. It is believed to act by modulation of glutamatergic transmission. Because the neurobiology of post-traumatic stress disorder (PTSD) has been hypothesized to involve alterations in glutamatergic transmission with subsequention neurotoxicity, we assessed the effects of phenytoin on cognition and brain structure in PTSD patients. Phenytoin was administered in an open label fashion for 3 months to nine adult patients with PTSD related to a variety of traumas, including early abuse, combat and car accidents. Subjects underwent magnetic resonance imaging for measurement of whole brain and hippocampal volume, and neuropsychological testing of memory and cognition, before and after treatment. Phenytoin treatment resulted in a significant 6% increase in right brain volume (p < 0.05). Increased hippocampal volume was correlated with reductions in symptom severity as measured by the Clinician Administered PTSD Scale and improvements in executive function as measured by the Trails test. However, treatment associated improvements in memory and cognition did not achieve statistical significance. These findings suggest that phenytoin treatment may be associated with changes in brain structure in patients with PTSD.

Background: Phenytoin is an anticonvulsant used in the treatment of epilepsy. Its mechanism of action is incompletely understood but most likely involves modulation of glutamatergic transmission. The neurobiology of posttraumatic stress disorder (PTSD) has been hypothesized to involve, at least in part, alterations in glutamatergic transmission in the hippocampus and possibly other brain regions. The purpose of this study was to assess the effects of phenytoin on symptoms of PTSD., Method: Phenytoin was administered in an open-label fashion for 3 months to 9 adult male and female patients with DSM-IV PTSD related to a variety of traumas including childhood abuse, combat, and car accidents. Dosage was adjusted to maintain the therapeutic blood levels used in the treatment of epilepsy. Subjects were assessed before, during, and after treatment for PTSD with standardized dimensional measures of disease severity including the Clinician Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton Rating Scale for Anxiety (HAM-A). Data were collected from November 2001 through June 2003., Results: Phenytoin treatment resulted in a significant decrease in PTSD symptoms as measured with the CAPS (mean score = 65 pretreatment vs. 38 posttreatment) with reductions in each of the symptom clusters of intrusions, avoidance, and hyperarousal (p < .05). There were no significant decreases in symptoms of depression severity as measured with the HAM-D or anxiety severity as measured with the HAM-A., Conclusions: These findings suggest that phenytoin may be efficacious in the treatment of PTSD, possibly mediated through its antiglutamatergic effects. Randomized, controlled, double-blind clinical trials are indicated to further evaluate this medication in the treatment of PTSD.

Study Objectives: (1) To describe a new percutaneous pleural biopsy technique to obtain multiple-site parietal pleural biopsy specimens in patients with pleural effusion (PE), and (2) to evaluate its effectiveness and safety compared to current techniques., Design: Prospective interventional study., Setting: University teaching hospital., Patients: Consecutively referred for evaluation of exudative PE., Intervention: With the patient in a semirecumbent position, a 9F sheath was inserted by the Seldinger technique into the pleural cavity on the midaxillary line under local anesthesia and fluoroscopic guidance. An 8F bioptome was introduced through it, and biopsy specimens were taken from several sites on the costal and diaphragmatic pleura. After biopsy, PE was completely evacuated, and the sheath was removed., Results: During the 2-year pilot study, we procured, on average, 14 adequate pleural specimens from each of the 28 patients (age range, 15 to 81 years) on the first attempt. Histopathologic examination revealed tuberculous pleuritis (18 patients), metastatic adenocarcinoma (1 patient), and nonspecific pleuritis (9 patients). Postprocedure, 25 patients had rapid symptomatic improvement without recurrence of PE. No major complications occurred during or after the procedure (mean follow-up period, 2 years)., Conclusions: Our new biopsy procedure can be performed easily, safely, and with increased diagnostic sensitivity and patient comfort. Unlike other biopsy techniques, it provides adequate multiple-site pleural biopsy specimens, in all cases, on the first attempt without any morbidity and mortality. It has a therapeutic potential to provide rapid symptomatic relief and treatment by pleurodesis. We recommend this procedure for patients whose conditions remain undiagnosed after undergoing needle biopsy or for those who cannot tolerate it, before considering more aggressive diagnostic interventions. This is the best alternative when thoracoscopy or thoracotomy are not available or when patients are at high risk for complications from them.

This paper is concerned with the interconnections between gender inequality and maternal deprivation, on the one hand, and the health of children (of either sex) and of adults that the children grow into (again, of either sex). The basic message of the paper is that women's deprivation in terms of nutrition and healthcare rebounds on the society as a whole in the form of ill-health of their offspring-males and females alike-both as children and as adults. There are a variety of pathways through which women's deprivation can affect the health of the society as a whole. This paper focuses on the pathways that operate through undernourishment of the mother. Maternal deprivation adversely affects the health of the fetus, which in turn leads to long-term health risks that extend not just into childhood but into adulthood as well. There are, however, important differences in the way children and adults experience the consequences of maternal deprivation via fetal deprivation. In particular, the pathways that lead to their respective risk factors and the circumstances under which those risk factors actually translate into ill-health are very different. These differences are best understood through the concept of 'overlapping health transition' in which two different regimes of diseases coexist side by side. Gender inequality exacerbates the old regime of diseases among the less affluent through the pathway of childhood undernutrition. At the same time it also exacerbates the new regime of diseases among the relatively more affluent through a pathway that has come to be known as the 'Barker hypothesis'. Gender inequality thus leads to a double jeopardy-simultaneously aggravating both regimes of diseases and thus raising the economic cost of overlapping health transition.

Objectives: To assess the feasibility of detecting new cases of heterozygous familial hypercholesterolaemia by using a nurse led genetic register., Design: Case finding among relatives of patients with familial hypercholesterolaemia., Setting: Two lipid clinics in central and south Manchester., Subjects: 259 (137 men and 122 women) probands and 285 first degree relatives., Results: Of the 200 first degree relatives tested, 121 (60%) had inherited familial hypercholesterolaemia. The newly diagnosed patients were younger than the probands and were generally detected before they had clinically overt atherosclerosis. Concentrations of serum cholesterol were, respectively, 8.4 (1.7 SD) mmol/l and 8.1 (1.9 SD) mmol/l in affected men and women and 5.6 (1.0 SD) mmol/l and 5.6 (1.1 SD) mmol/l in unaffected men and women. Screening for risk factors as recommended in recent guidelines for coronary heart disease prevention would have failed to identify most of the affected relatives in whom hypertension, diabetes mellitus, cigarette smoking, and obesity were uncommon., Conclusions: By performing cholesterol tests on 200 relatives, 121 new patients with familial hypercholesterolaemia were discovered. Because 1 in 500 people in the United Kingdom are affected by this condition, to detect a similar number by population screening over 60 000 tests would be required, and only a few of these patients would have been detected had cholesterol testing been restricted to those with other risk factors for coronary heart disease. A case exists for organising a genetic register approach, linking lipid clinics nationally.

With the new myocardial agent Tc-99m sestamibi, relatively high abdominal uptake represents a major limiting factor. The effect of a standard feeding (commercial milkshake taken immediately after injection), and posture (standing versus sitting for 10 minutes postinjection) on the resting biodistribution of sestamibi was investigated in patients receiving 3 to 5 MBq/kg injections as part of rest-stress tomography. Ancillary anterior 1-minute images of heart and abdomen were obtained at 15 minutes postinjection and 90 to 140 minutes postinjection in 32 patients, randomized to feeding and postural treatments. Feeding decreased the activity in the gallbladder at both 15 and 110 minutes, but had no effect on liver parenchyma; activity in a background rectangle immediately beneath the heart was decreased by feeding only on the 15-minute images. An effect of posture was not apparent. Further study of the acute effects of a milkshake in eight patients showed a prompt reduction of 26% in a subdiaphragmatic background rectangle, but a more gradual decline in gallbladder counts. Thus, feeding of lipid after injection is not an essential component of sestamibi imaging protocols; oral administration of fluid immediately before imaging may help reduce interfering gastric activity.