Accuracy in osteotomy drilling using a new universal and disposable drill-stop device for dental implant drills: an in vitro study using a bovine rib model.

BACKGROUND: This study aimed to evaluate the surgical accuracy of a new universal disposable stop system for implant drills (FCA Universal Drill Stop). MATERIAL AND METHODS: A total of 60 bovine ribs were included in this in vitro study. The ribs were randomized into three study groups (n=20 ribs per group). In each study group (Group1: drills without stop or control group, Group 2: prefabricated drills with stop or gold standard group, and Group 3: drills with FCA Universal Drill Stop) a total of 100 osteotomies were performed with implant drills in each group, following the drilling sequence for the placement of a dental implant of 10 mm length and 4 mm diameter. The accuracy of the depth of the osteotomies was quantified clinically (with periodontal probe) and radiologically, using ImageJ version 1.48v software. RESULTS: The order of highest to lowest accuracy (clinical and radiological) in the depth of osteotomies was: FCA Universal Drill Stop> prefabricated drills with a stop>drills without stop, with statistically significant differences being observed between both systems with stop with respect to the control group, although not between them. CONCLUSIONS: The new universal disposable stop system for implant drills, offers similar accuracy to prefabricated drills with stop, with both systems being much more accurate than implant drills without stop. Although this experimental evaluation showed favourable results, further clinical studies are necessary.

Immune cell arrival kinetics to peritoneum and role during murine-experimental trichomoniasis.

Trichomonas vaginalis causes trichomoniasis, an inflammatory process related to an increased rate of HIV transmission. In order to study T. vaginalis infection response in a microorganism-free environment, an infection model was established providing a host­parasite interaction system useful to study the interplay between immune cells and the parasite. Infected mice peritoneal cells were immunophenotyped at different times after infection using flow cytometry. Neutrophils and macrophages showed the most relevant increase from third to 12th day post-infection. A high number of B lymphocytes were present on 15th day post-infection, and an increase in memory T cells was observed on sixth day post-infection. The levels of NO increased at day 10 post-infection; no significant influence was observed on T. vaginalis clearance. Increased viability of T. vaginalis was observed when the NETs inhibitors, metformin and Cl− amidine, were administrated, highlighting the importance of this mechanism to control parasite infection (43 and 86%, respectively). This report presents a comprehensive cell count of the immune cells participating against trichomoniasis in an in vivo interaction system. These data highlight the relevance of innate mechanisms such as specific population changes of innate immune cells and their impact on the T. vaginalis viability.

Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

Intensification of treatment with pegylated interferon alfa in patients coinfected with HIV and HBV genotype H or G being treated with a tenofovir/emtricitabine-containing regimen.

BACKGROUND/AIMS: The most common HBV genotypes in HIV-coinfected patients in Mexico are H and G; the response to treatment for these genotypes is unknown. The aim of the study was to examine the effectiveness of intensification with pegylated interferon (PEG-IFN) alfa-2a or alfa-2b in HBV/HIV-coinfected patients treated with a tenofovir/emtricitabine (TDF/FTC) backbone in an HIV clinic in Mexico City. METHODOLOGY: We performed a single-arm open-label trial involving HBV/HIV-coinfected patients. Patients with chronic hepatitis B who were HBeAg positive were treated with TDF/FTC-containing regimen. Treatment was intensified by addition of PEG-IFN alfa-2b or alfa-2a for 24 weeks. The primary endpoint of effectiveness, assessed after 24 weeks, was suppression of HBV DNA to <60 IU/mL. RESULTS: We enrolled 29 patients; 27 (93%) were men. HBV genotypes were F in 2 (6.9%), A in 2 (6.9%), G in 10 (34.5%), and H in 15 (51.7%). The primary endpoint was present in 17 (58%) patients (95% CI 29.7%­70.8%). CONCLUSIONS: Intensification with PEG-IFN alfa-2a or alfa-2b is effective and well tolerated in patients with chronic hepatitis B who are HBeAg positive, have genotype H or G, and are coinfected with HIV while they are being treated with TDF/FTC-containing regimen.

The MAPP Room Memory Test: Examining Contextual Memory Using a Novel Computerized Test in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer's Disease.

Contextual memory, the ability to remember spatial or temporal features related to an event, is affected in Alzheimer's disease (AD). There is a shortfall of tests that measure contextual memory. To evaluate visuospatial contextual memory, we developed a computerized cognitive test, the MAPP Room Memory Test, which requires participants to identify in which visual scene target items were previously presented. We hypothesized that cognitively-unimpaired carriers of an autosomal dominant AD mutation (Presenilin-1 E280A, n=15) would perform more poorly on this test than non-carrier family members (n=31). Compared to non-carriers, the carriers had significantly worse delayed room recognition. The results indicate that the MAPP Room Memory Test may be sensitive to subtle cognitive changes associated with risk of AD. Future studies with larger samples using the MAPP Room Memory Test and biomarkers are needed to examine whether this test may also be sensitive to the earliest pathological changes in preclinical AD.

Functional associations of genetic variants involved in the clinical manifestation of erythropoietic protoporphyria in the Argentinean population.

BACKGROUND: Combined inheritance of genetic variants in ferrochelatase gene (FECH) are implicated in clinical manifestation of Erythropoietic Protoporphyria (EPP). OBJECTIVE: Identify the genetic variants in FECH gene and their associations in the expression of EPP in Argentina. Determine the allelic frequency of polymorphic variants, associations in cis and its linkage disequilibrium. METHODS: The FECH gene was PCR-amplified and sequenced. Allelic variants of intragenic polymorphisms were identified by PCR followed by sequencing or restriction digestion analysis. Residual FECH activity was determined by prokaryotic expression in Escherichia coli JM109. Data were analyzed using Haploview and Statistix 9. RESULTS: Ten mutations were identified: three novel (p.S222N; p.R298X and p.R367X) and seven already known (g.12490_18067del; p.R115X; p.I186T; c.580_584delTACAG; c.598 + 1 G>T; p.Y209X and p.W310X). The p.R115X mutation was found in two families. The p.S222N mutation expressed 5% of normal activity. Only individuals who inherited a mutation combined in trans to a low expression allele c.1-251G, c.68-23T, and c.315-48C, showed clinical symptoms. The absence of c.315-48C variant was sufficient for not triggering EPP. However, these variants showed high levels of cosegregation and GTC haplotype is over-represented in EPP patients. CONCLUSION: In the dominant inheritance form of EPP, c.315-48C variant in trans to the mutated allele is sufficient to trigger the disease. The presence of GTC haplotype in all patients with dominant EPP could be due to the high level of cosegregation of c.315-48C with c.1-251G and c.68-23T variants in our population.

Memory for Semantically Related Objects Differentiates Cognitively Unimpaired Autosomal Dominant Mutation Carriers from Non-Carrier Family Members.

Early cognitive changes due to Alzheimer's disease (AD) include difficulties in semantic access and working memory. Using a computerized cognitive test developed by our group, called the Memory for Semantically Related Objects test (MESERO), we evaluated if cognitively unimpaired carriers of an autosomal dominant AD (ADAD) mutation performed worse on this test than non-carrier family members. 35 cognitively unimpaired ADAD mutation carriers and 26 non-carrier family members from a Colombian ADAD cohort took the MESERO on a laptop computer. Cognitively unimpaired ADAD carriers had significantly worse MESERO total scores than non-carrier family members, driven by worse performance in semantically-related object sets; group performances did not differ on semantically unrelated object sets. Findings suggest that MESERO performance may be sensitive to subtle cognitive changes associated with AD. Future MESERO research should examine performances between healthy older adults and people at risk for sporadic AD.

Electrospun Polyvinylpyrrolidone-Gelatin and Cellulose Acetate Bi-Layer Scaffold Loaded with Gentamicin as Possible Wound Dressing.

Acceleration of wound healing can be achieved with the use of wound dressings. Through the electrospinning technique, a polymeric scaffold composed of two layers was processed: a gelatin and polyvinylpyrrolidone layer with gentamicin, and a second layer of cellulose acetate. The conditions for the electrospinning process were standardized for voltage parameters, feed flow and the distance from the injector to the collector. Once the values of the main variables for the electrospinning were optimized, a three-hour processing time was established to allow the separation of the material from the collector. The obtained material was characterized by observations on scanning electron microscopy, Fourier transform infrared spectroscopy and thermal analysis; contact angle measurement was performed to evaluate wettability properties, and antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus were evaluated using the Kirby-Bauer test. The obtained fibers that form the bi-layer scaffold present diameters from 100 to 300 nm. The scaffold presents chemical composition, thermal stability, wettability characteristics and antibacterial activity that fulfill the proposal from this study, based on obtaining a scaffold that could be used as a drug delivery vehicle and a wound dressing material.

SEOM clinical guidelines in hereditary breast and ovarian cancer (2019).

Mutations in BRCA1 and BRCA2 high penetrance genes account for most hereditary breast and ovarian cancer, although other new high-moderate penetrance genes included in multigene panels have increased the genetic diagnosis of hereditary breast and ovarian cancer families by 50%. Multigene cancer panels provide new challenges related to increased frequency of variants of uncertain significance, new gene-specific cancer risk assessments, and clinical recommendations for carriers of mutations of new genes. Although clinical criteria for genetic testing continue to be largely based on personal and family history with around a 10% detection rate, broader criteria are being applied with a lower threshold for detecting mutations when there are therapeutic implications for patients with breast or ovarian cancer. In this regard, new models of genetic counselling and testing are being implemented following the registration of PARP inhibitors for individuals who display BRCA mutations. Massive sequencing techniques in tumor tissue is also driving a paradigm shift in genetic testing and potential identification of germline mutations. In this paper, we review the current clinical criteria for genetic testing, as well as surveillance recommendations in healthy carriers, risk reduction surgical options, and new treatment strategies in breast cancer gene-mutated carriers.

Association of QRS Complex Fragmentation with QT Interval Prolongation in Patients with Ischemic Heart Disease.

BACKGROUND: The fragmented QRS complex (FQRS) was found to be associated to malignant ventricular arrhythmias and sudden death in patients with hypertrophic cardiomyopathy and other entities. There is scant data available correlating the presence of FQRS with QT interval prolongation in patients with ischemic heart disease (IHD). METHODS: A descriptive, retrospective, cross-sectional study was performed in 123 patients with IHD to analyze and correlate the presence of FQRS with QT interval prolongation in the conventional 12-leads electrocardiogram in patients with documented chronic IHD. RESULTS: There were 62% male patients. The mean age was 63.8±12.6 years. Thirty six (44%) patients had fragmented QRS (64% men and 36% women). The duration of QT and QTc, the mean values were 413±59ms, and 463±67ms, respectively. Of the 36 patients with FQRS, 23 patients have prolongation of the QTc interval, and 13 patients did not present it. Of the 45 patients without FQRS, 21 of them have prolongation of the QTc interval, and 24 patients did not have it. These data resulted in a sensitivity of 52% with a moderate SnNout, a specificity of 65% with moderate SpPin, a positive predictive accuracy of 64%, a negative predictive accuracy of 53%. These data resulted in a prevalence of 54%. CONCLUSION: the presence of FQRS in the ECG has a moderate sensitivity and specificity, as well as, moderate negative and positive predictive value of the existence of QT interval prolongation in patients with ischemic heart disease.

SEOM-SERAM-SEMNIM guidelines on the use of functional and molecular imaging techniques in advanced non-small-cell lung cancer. / Guía SEOM-SERAM-SEMNIM sobre el empleo de las técnicas de imagen funcional y molecular en el cáncer de pulmón no microcítico avanzado.

Imaging in oncology is an essential tool for patient management but its potential is being profoundly underutilized. Each of the techniques used in the diagnostic process also conveys functional information that can be relevant in treatment decision making. New imaging algorithms and techniques enhance our knowledge about the phenotype of the tumor and its potential response to different therapies. Functional imaging can be defined as the one that provides information beyond the purely morphological data, and include all the techniques that make it possible to measure specific physiological functions of the tumor, whereas molecular imaging would include techniques that allow us to measure metabolic changes. Functional and molecular techniques included in this document are based on multi-detector computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), magnetic resonance imaging (MRI), and hybrid equipments, integrating PET with CT (PET/CT) or MRI (PET-MRI). Lung cancer is one of the most frequent and deadly tumors although survival is increasing thanks to advances in diagnostic methods and new treatments. This increased survival poises challenges in terms of proper follow-up and definitions of response and progression, as exemplified by immune therapy-related pseudoprogression. In this consensus document, the use of functional and molecular imaging techniques will be addressed to exploit their current potential and explore future applications in the diagnosis, evaluation of response and detection of recurrence of advanced NSCLC.

SEOM-SERAM-SEMNIM guidelines on the use of functional and molecular imaging techniques in advanced non-small-cell lung cancer.

Imaging in oncology is an essential tool for patient management but its potential is being profoundly underutilized. Each of the techniques used in the diagnostic process also conveys functional information that can be relevant in treatment decision-making. New imaging algorithms and techniques enhance our knowledge about the phenotype of the tumor and its potential response to different therapies. Functional imaging can be defined as the one that provides information beyond the purely morphological data, and include all the techniques that make it possible to measure specific physiological functions of the tumor, whereas molecular imaging would include techniques that allow us to measure metabolic changes. Functional and molecular techniques included in this document are based on multi-detector computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), magnetic resonance imaging (MRI), and hybrid equipments, integrating PET with CT (PET/CT) or MRI (PET-MRI). Lung cancer is one of the most frequent and deadly tumors although survival is increasing thanks to advances in diagnostic methods and new treatments. This increased survival poises challenges in terms of proper follow-up and definitions of response and progression, as exemplified by immune therapy-related pseudoprogression. In this consensus document, the use of functional and molecular imaging techniques will be addressed to exploit their current potential and explore future applications in the diagnosis, evaluation of response and detection of recurrence of advanced NSCLC.

Low dose gemcitabine plus cisplatin in a weekly-based regimen as salvage therapy for relapsed breast cancer after taxane-anthracycline-containing regimens.

PURPOSE: Cisplatin-gemcitabine is a synergistic chemotherapy (CT) combination highly proven in a broad spectrum of epithelial neoplasms and shows a non-cross-resistance profile with the most active drugs in metastatic breast cancer (MBC). We have conducted an exploratory study to determine if treatment with low doses of a combination of fixed-rate gemcitabine infusion and cisplatin was clinically meaningful in women relapsing after a minimum of 2 prior lines of CT for advanced disease (range 2-6), which had to have necessarily included both anthracyclines and taxanes. Another goal was to find the optimal individual schedule by adjusting frequency and dosage according to patient tolerability. PATIENTS AND METHODS: From May 2002 to November 2003, 22 patients with relapsed advanced BC and a minimum of two prior CT lines were offered treatment with gemcitabine (G) (initial dose 750 mg/m(2), or 600 mg/m(2) if the patient had received more than two previous CT lines) plus cisplatin (P) (initial dose 30 mg/m(2), or 20 mg/m(2) in case of > or =3 prior CT lines) on days 1 and 8 of a 21-day cycle. Treatment was postponed to day 15 if it could not be given on day 8, without dose reduction. If treatment could not be given on day 15, a 20% dose reduction was allowed and treatment given the next week. Further dose reductions were allowed as needed up to a maximum of three. Treatment continued until disease progression or intolerable toxicity. Median age was 54.5 years (35-75). Median Karnofsky was 90 (range 80-90). Median number of prior CT lines was 3 (2-6). 90.9% of patients had received adjuvant CT. All had prior anthracyclines and taxanes. Other agents used included 5-FU/eniluracil, MTA, RPR 109881A, trastuzumab, cisplatin, VP16, vinorelbine, capecitabine and irinotecan. 72.7% had received radiotherapy and 68.1% hormonal therapy (median 2 lines, range 1-4). RESULTS: Partial responses (PR) were seen in 9.1% of patients and stable disease (SD) in 36.4%. Clinical Benefit Rate (PR+SD) was derived in 45.5% of patients. Median time to progression was 4 months (95% CI, 3-5) in general and 6 months (95% CI, 4-8) in patients with clinical benefit. Median survival for the entire group was 8 months (95% CI, 5-11) and 19 months when clinical benefit was obtained (95% CI, 11-25). Patients received a median of 8.5 CT administrations (range, 2-45). Forty-three percent of doses were delayed. Sixteen out of 22 patients needed a delay and/or reduction of initial dose. Cisplatin and gemcitabine doses were reduced in 75% and 62% of all cycles, respectively. Sixteen out of 22 patients needed a delay and/or reduction of initial dose. Toxicities grade >3 were neutropenia 35% and thrombocytopenia 15%. All other toxicities were grade 2 or less, including sensorial neuropathy (30%), asthenia (34%), nausea/vomiting (20%) and oral mucositis (15%). There were no treatment-related deaths. Reasons for discontinuation were progression (18 patients), death (3 patients) and patient decision (1 patient). CONCLUSION: Weekly cisplatin-gemcitabine with flexible downwards individual tailoring is a safe and effective salvage treatment in heavily pretreated MBC patients with good PS.

[Degenerative espondylolisthesis. Body mass index influence on the post-surgical evolution]. / Espondilolistesis degenerativa. Influencia del índice de masa corporal en la evolución postquirúrgica.

Spondylolisthesis is the sliding of a vertebral body with respect to the adjacent one. According to the degree of slippage it is classified into 4 Meyerding grades. Patients with spondylolisthesis who underwent surgery with lumbar instrumentation were included. They were divided into two groups based on their body mass index: obese and non-obese. The functional capacity Oswestry score was calculated preoperatively and at one year, and it was correlated with the BMI. A total of 46 patients, 26 females and 20 males, were included, from 2010 to 2013, all of them with a diagnosis of degenerative spondylolisthesis with lumbar stenosis. Mean age was 58.9 years. The mean preoperative Oswestry disability index was 41% in non-obese patients and 47% in obese patients. At the one-year postoperative assessment the disability index was 12.30% in non-obese patients and 23.84% in obese patients. Non-obese patients had a more favorable clinical course compared to the group of obese patients.

La espondilolistesis es el desplazamiento de un cuerpo vertebral en relación con el adyacente, el cual se clasifica en cuatro grados según Meyerding. Se incluyeron pacientes con espondilolistesis sometidos a manejo quirúrgico con instrumentación lumbar, mismos que se dividieron en dos grupos de acuerdo con su índice de masa corporal en obesos y no obesos. Se les aplicó un cuestionario Oswestry de capacidad funcional de forma prequirúrgica y al año de evolución se midió la correlación entre éste y el IMC. Se incluyeron 46 pacientes, 26 mujeres y 20 hombres de 2010 a 2013, con diagnóstico de espondilolistesis degenerativa con canal lumbar estrecho. La edad promedio fue de 58.9 años. El promedio del índice de discapacidad de Oswestry prequirúrgico en los pacientes no obesos fue 41% y en los pacientes obesos fue 47% con un año de seguimiento postquirúrgico con índice de discapacidad en no obesos de 12.30% y en obesos de 23.84%. El grupo de pacientes no obesos presentó una evolución clínica más favorable comparado con el grupo de pacientes con obesidad.

Obstruction in extracardiac ventriculopulmonary conduits: value of nuclear magnetic resonance imaging with velocity mapping and Doppler echocardiography.

OBJECTIVES: This study was designed to investigate the value of noninvasive imaging modalities for the detection of obstruction in extracardiac ventriculopulmonary conduits. BACKGROUND: the diagnosis of obstruction in a conduit by noninvasive methods can be difficult. Obstruction may be silent and its progression unnoticed. Nuclear magnetic resonance imaging (NMR) with velocity mapping is a new noninvasive technique that can provide high resolution images and has been shown to be a reliable method of measuring blood flow velocity. METHODS: Two-dimensional echocardiography, pulsed wave Doppler echocardiography and NMR spin echo imaging were used in 52 patients with an extracardiac ventriculopulmonary conduit. Continuous wave Doppler echocardiography was used in 30 of these, Doppler color flow mapping in 26 and NMR velocity mapping in 12. Cardiac catheterization data were available in 27 patients and operative or autopsy findings in 11. RESULTS: The conduit could be assessed by two-dimensional and pulsed wave Doppler echocardiography in only 17% of patients. Doppler color flow and continuous wave echocardiography provided technically satisfactory data in 19% and 83%, respectively. The anatomy of the conduit was adequately displayed by NMR imaging in 90%. A minimal diameter less than 18 mm indicated conduit obstruction, although failure to detect calcification resulted in obstruction being missed in some patients. Calculated gradients in obstructed conduits derived from NMR velocity mapping correlated well with results of continuous wave Doppler echocardiography and gave an accurate localization of the site of obstruction as well as a measure of its severity. CONCLUSION: NMR imaging with velocity mapping is the most effective noninvasive method of assessing obstruction in ventriculopulmonary conduits and can obviate the need for invasive investigation before an interventional procedure is performed.

Preventive treatments for breast cancer: recent developments.

Breast cancer is a burden for western societies, and an increasing one in emerging economies, because of its high incidence and enormous psychological, social, sanitary and economic costs. However, breast cancer is a preventable disease in a significant proportion. Recent developments in the armamentarium of effective drugs for breast cancer prevention (namely exemestane and anastrozole), the new recommendation from the National Institute for Health and Care Excellence to use preventative drugs in women at high risk as well as updated Guidelines from the US Preventive Services Task Force and the American Society of Clinical Oncology should give renewed momentum to the pharmacological prevention of breast cancer. In this article we review recent major developments in the field and examine their ongoing repercussion for breast cancer prevention. As a practical example, the potential impact of preventive measures in Spain is evaluated and a course of practical actions is delineated.

Genotypic polymorphisms in experimental metastatic dermal leishmaniasis.

Molecular karyotype and kDNA restriction analyses were utilized to examine the genetic heterogeneity and plasticity of the Leishmania (Viannia) guyanensis strain WHI/BR/78/M5313, composed of metastatic and non-metastatic populations. Cloning revealed that the strain was constituted by multiple closely related populations that were distinguishable by restriction fragment polymorphisms in kDNA. Size polymorphisms in molecular karyotype were not detected. Passage of clones in hamsters and recovery of parasites from cutaneous metastatic lesions yielded evidence of further genetic heterogeneity among some of the progeny populations. Overall, six kDNA minicircle restriction patterns or schizodemes were observed among clones, subclones and progeny. Although the possibility that population heterogeneity was not resolved by cloning cannot be ruled out, subcloning and kDNA restriction analysis to determine whether the putative clones consisted of homogeneous populations showed the schizodeme of subclones of 3 out of 4 clones to be identical to the clone of origin, while a subclone of the fourth had a co-efficient of similarity of 0.95. Metastasis did not segregate with a particular schizodeme: all six restriction profiles were represented among populations isolated from metastatic lesions and some clones with the same restriction profile did not produce metastatic lesions. The strain from which the clones, subclones and progeny were derived had a kDNA restriction pattern identical to the most prevalent schizodeme (38%) among these subpopulations. This finding together with the reappearance of the repertoire of schizodemes found among clones in the populations recovered from metastatic lesions in hamsters inoculated with a single clone, suggest that sequence polymorphisms in kDNA can emerge during infection.

Prenatal detection of de novo duplication of the short arm of chromosome 18 confirmed by fluorescence in situ hybridization (FISH).

We present a patient with developmental delay, minor anomalies, and duplication 18p confirmed by fluorescence in situ hybridization with whole chromosome 18 painting probe (Oncor p5218). Our observation confirms the findings of other investigators that duplication 18p is not associated with major malformations.

1p microdeletion in sibs with minimal phenotypic manifestations.

We report on two sibs with a paracentric inversion of chromosome 1 [inv(1)(p22.3p34.1)] and a small deletion of the same chromosome (p34.1-->p34.3). They presented with learning disabilities and disturbed conduct but lacked the more severe manifestations usually associated with autosomal chromosome deletion. Born to an alcoholic mother and later placed in foster care because of abuse and neglect, the behavior abnormalities they present are likely to be associated with their traumatic postnatal experience. Microscopic deletions without significant morphological phenotypic expression have been described but are rarely reported. Most reported cases of interstitial deletion of 1p had associated malformations and psychomotor retardation. These sibs may represent the first evidence that deletion of 1p34.1-->1p34.3 may have little impact on the phenotype.

Adrenal insufficiency in Smith-Lemli-Opitz syndrome.

We describe three unrelated patients with adrenal insufficiency and RSH or Smith-Lemli-Opitz syndrome (SLOS), a disorder due to deficient synthesis of cholesterol. These patients presented with hyponatremia, hyperkalemia, and decreased aldosterone-to-renin ratio, which is a sensitive measure of the renin-aldosterone axis. All patients had profound serum total cholesterol deficiency (14-31 mg/dl) and marked elevation of 7-dehydrocholesterol (10-45 mg/ dl). Two patients were newborn infants with 46, XY karyotypes and complete failure to masculinize; one of these patients also had cortisol deficiency. Both patients died within 10 days of birth of cardiopulmonary complications while on adrenal replacement therapy. The third patient diagnosed with SLOS at birth presented at age 7months with fever and diarrhea and was noted to have profound hyponatremia. This patient is maintaining normal serum electrolytes on mineralocorticoid replacement. We conclude that adrenal insufficiency may be a previously undetected and treatable manifestation in SLOS. We hypothesize that deficiency of cholesterol, an adrenal hormone precursor, may lead to insufficient synthesis of adrenal steroid hormones.