Revealing the spatial distribution of a disease while preserving privacy

Datasets describing the health status of individuals are important for medical research but must be used cautiously to protect patient privacy. For patient data containing geographical identifiers, the conventional solution is to aggregate the data by large areas. This method often preserves privacy but suffers from substantial information loss, which degrades the quality of subsequent disease mapping or cluster detection studies. Other heuristic methods for de-identifying spatial patient information do not quantify the risk to individual privacy. We develop an optimal method based on linear programming to add noise to individual locations that preserves the distribution of a disease. The method ensures a small, quantitative risk of individual re-identification. Because the amount of noise added is minimal for the desired degree of privacy protection, the de-identified set is ideal for spatial epidemiological studies. We apply the method to patients in New York County, New York, showing that privacy is guaranteed while moving patients 25—150 times less than aggregation by zip code.     

Adipocytokines: leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come

With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they are increasingly shown to affect several aspects in the pathogenesis of obesity-related diseases. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centred in the hypothalamus. In recent years, a number of additional signalling molecules secreted by adipose tissue have been discovered, commonly referred to as 'adipocytokines'. Among these, adiponectin is perhaps the most interesting and promising compound for the clinician since it has profound protective actions in the pathogenesis of diabetes and cardiovascular disease. Adiponectin is low in obese subjects and, in particular, insulin-resistant patients. In contrast, resistin seems to be of greater relevance in relation to the immune stress response than in the regulation of glucose homeostasis. However, inflammatory processes have recently been connected with the development of atherosclerosis. Finally, little is known regarding the clinical relevance of visfatin. Recent research has revealed many functions of adipocytokines extending far beyond metabolism, such as immunity, cancer and bone formation. This report aims to review some of the recent topics of adipocytokine research that may be of particular importance.     

Update in Outpatient General Internal Medicine: Practice-Changing Evidence Published in 2020

In a time of rapidly shifting evidence-based medicine, it is challenging to stay informed of research that modifies clinical practice. To enhance knowledge of practice-changing literature, a group of 7 internists reviewed titles and abstracts in 7 internal medicine journals with the highest impact factors and relevance to outpatient general internal medicine. Coronavirus disease-19 research was purposely excluded to highlight practice changes beyond the pandemic. New England Journal of Medicine (NEJM), The Lancet, Annals of Internal Medicine, Journal of the American Medical Association (JAMA), JAMA Internal Medicine, British Medical Journal (BMJ), and Public Library of Science (PLoS) Medicine were reviewed. The following collections of article synopses and databases were also reviewed: American College of Physicians Journal Club, NEJM Journal Watch, BMJ Evidence-Based Medicine, McMaster/DynaMed Evidence Alerts, and Cochrane Reviews. A modified Delphi method was used to gain consensus based on relevance to outpatient internal medicine, impact on practice, and strength of evidence. Clusters of articles pertaining to the same topic were considered together. In total, 7 practice-changing articles were included.     

Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism

OBJECTIVE: To determine the frequency of mutations of the gonadotropin-releasing hormone receptor (GnRHR) and of the G protein-coupled receptor 54 (GPR54) genes in normosmic idiopathic hypogonadotropic hypogonadism (IHH). METHODS: In a retrospective study we analyzed the GnRHR and the GPR54 genes of 45 IHH patients and 50 controls. Genomic DNA was amplified by PCR to obtain partially overlapping amplicons encompassing the exon-intron boundaries of the GnRHR and GPR54 genes and analyzed by single-stranded conformation polymorphism gel electrophoresis and/or DNA sequencing. RESULTS: One heterozygous R262Q mutation of the GnRHR gene was identified in one patient with familial IHH. The silent single-nucleotide polymorphism (SNP) 453C > T occurred at the same frequency in patients and controls. One patient with sporadic IHH and consanguineous parents showed a novel homozygous sequence variation of the GPR54 gene (1001_1002insC) resulting in an open reading frame shift and elongation of 43 amino acids with an increased number of proline residues in the intracellular receptor domain. This patient had delayed puberty, low testosterone (3.4 nmol/l), and low-normal LH and FSH levels responsive to GnRH. Pulsatile GnRH administration normalized testosterone levels and induced spermatogenesis sufficiently to induce a pregnancy with assisted reproduction. Two common SNPs in exon 1 and exon 5 of the GPR54 gene showed similar frequency distribution and hormonal profiles in IHH and controls. CONCLUSIONS: Mutations of the GnRHR and of the GPR54 gene are rare in IHH and should be investigated especially in cases with autosomal recessive transmission. Common SNPs of the GnRHR and GPR54 genes do not play any role in IHH.     

Predictors of restenosis after treatment of bifurcational lesions with paclitaxel eluting stents: a multicenter prospective registry of 150 consecutive patients.

OBJECTIVES: The aim of the study was the assessment of the clinical, angiographic and procedural characteristics correlated with freedom from adverse events at 1 year in a real life setting of consecutive bifurcation lesions. BACKGROUND: Even if stent implantation has shown to be superior to conventional balloon angioplasty in most coronary lesions, bifurcation treatment with stent implantation both in main and in side branch (SB) still raises controversy. METHODS: We reviewed the results obtained in a prospective multicenter registry of 150 patients with 158 bifurcation lesions involving a SB of sufficient diameter to be treated, if necessary, with a polymer based paclitaxel eluting stent (PES, TAXUS). Two stents were used in 118 lesions (74.7%). Final kissing balloon inflation was performed in 87/118 lesions (73.7%) and in 30/40 lesions (75.0%) of the 2 and 1 stent group respectively. RESULTS: At 1-year clinical follow-up we observed 4 stent thromboses, all involving the SBs of the 2 stents group (2.7%). Unlike previous reports, revascularization involved the main vessel in the majority of patients (21/150, 14.0%). After an exploratory multivariable analysis the only parameter predictive of target lesion revascularization (TLR) (HR 0.52; CI 95% 0.11-0.86; p = 0.02) and target vessel revascularization (TVR) (HR 0.47; CI 95% 0.14-0.90; p = 0.03) was postprocedural main branch minimal lumen diameter (MB-MLD). CONCLUSIONS: In a real life setting of consecutive bifurcation lesions, thrombosis rate, concentrated in the SB and the 2-stents group, and need for target lesion revascularization remain higher than in less complex lesion subgroups treated with PES. No differences in immediate success and TLR were observed between 2 stents and 1 stent groups. The frequently observed suboptimal stent expansion and final MB-MLD predict 1 year revascularization.     

R56865, a Na- and Ca-Overload Inhibitor, Reduces Myocardial Ischemia-Reperfusion Injury in Blood-Perfused Rabbit Hearts

The cardioprotective effects of R56865 were studied in isolated rabbit hearts, blood-perfused with a support rabbit system. The effect on ischemic injury was evaluated by comparing myocardial contracture and contents of ATP catabolites and of lactate during 60 min of normothermic ischemia in untreated hearts (group I) and in hearts treated with 0.63 mg/kg of R56865 starting 20 min before ischemia (group II; n = 5 in each group). R56865 delayed the onset, and decreased the extent of ischemic contracture, but had no effect on the myocardial content of ATP, of its catabolites or of lactate. The effect on reperfusion injury was studied by monitoring left ventricular function during 80-min reperfusion after the 60-min ischemia in three groups (n = 6 in each): an untreated group (group I) and two groups treated with R56865 given either before (group II) or after ischemia (group III). Ultrastructural changes and cellular calcium distribution after reperfusion were also studied. R56865 improved the recovery of function and prevented contracture during reperfusion. Left ventricular end-diastolic pressure was 13.2 ± 2.8 mmHg in group II and 31.3 ± 8.1 mmHg in group III vs 45.0 ± 2.6 mmHg in group I (P < 0.0001 for II vs I; P > 0.05 for III vs I). Left ventricular developed pressure, maximum dP/dt and minimum dP/dt recovered to 71.0 ± 5.4%, 98.9 ± 6.1%, 85.3 ± 4.8% of baseline values, respectively, in group II, to 64.5 ± 3.0% (P > 0.05), 76.8 ± 3.0%, 70.2 ± 4.0% in group III, vs 52.0 ± 6.5%, 58.9 ± 6.9% and 53.6 ± 5.8% in untreated hearts (P < 0.05 for II or III vs I). Coronary flow was 24.5 ± 2.2 ml/min and 19.8 ± 1.8 ml/min in groups II and III vs 14.8 ± 0.7 ml/min (P < 0.05) in the untreated group. On histology the myocardium in hearts treated either before after ischemia was well protected and calcium distribution was almost normal after reperfusion, while in untreated hearts, most of the myocardium displayed irreversible damage accompanied by massive intracellular calcium accumulation. We conclude that R56865 could attenuate Ca²⁺-overload, thereby reducing myocardial ischemia-reperfusion injury after an extended period of ischemia.     

Die chromosomalen Veränderungen in der Rattenleber während der krebsigen Entartung nach Verfütterung von Buttergelb

Zusammenfassung Erwachsene Ratten wurden mit 4-Dimethylaminoazobenzol (“Buttergelb”) gefüttert und die Mitosen der Leberkerne nach Aufnahme verschiedener Buttergelbmengen (200–1020 mg) auf Chromosomenzahlen und Mitoseanomalien hin untersucht. Um mehr Teilungsstadien zu erhalten, wurde die Leber 48 Std vor der Fixierung partiell hepatektomiert. Auch in buttergelbbehandelten Rattenlebern ist ein Mitosemuster vorhanden, dessen Zusammensetzung sich w?hrend der Buttergelbbehandlung in charakteristischer Weise ver?ndert: Mit steigender Buttergelbdosis nehmen die diploiden Mitosen stark ab (von 44% auf 10%), die aneuploiden Stadien stark zu (von 13% auf 60%). Die Ver?nderungen vom euploiden (diploiden) zum aneuploiden Mitosemuster gehen sprunghaft vor sich, wobei die erste Reaktionsschwelle nach 300 mg Buttergelbaufnahme liegt. Bei 939 untersuchten aneuploiden Metaphasen finden sich Chromosomenzahlen zwischen 6 und 192. Von den in diesem Bereich enthaltenen 178 m?glichen aneuploiden Zahlen sind nur 50 realisiert. Die Zahlen 27, 33, 36, 48, 54, 69, 75, 96 sind dabei besonders h?ufig (78,5% aller aneuploiden Metaphasen). Mit steigender Buttergelbdosis kommen zus?tzlich zu den bereits bevorzugt auftretenden vier aneuploiden Zahlen der unbehandelten Leber weitere aneuploide Zahlen als bevorzugt hinzu, deren H?ufigkeit mit steigender Dosis ansteigt. Ferner treten neue aneuploide, nicht bevorzugte Chromosomenzahlen auf. Sowohl für die neuauftretenden, bevorzugten wie nicht bevorzugten Klassen ist eine an bestimmte Buttergelbdosen gebundene Entstehung charakteristisch. Mit 4 Textabbildungen     

Dysphagia after pharyngolaryngeal cancer surgery. Part I: Pathophysiology of postsurgical deglutition

Eighty-one patients were examined after laryngopharyngeal cancer surgery with a sequential computer manometry system using 4-channel-pressure probes. The general swallowing coordination is neither a matter of the oropharyngeal pressure thrust nor of the pharyngeal transit time, but mainly depends on swallowing initiation. The points of interest are both the pharyngeal inlet and outlet. The topographic correlates are the base of the tongue and the upper esophageal sphincter (UES). Resections of the base of the tongue lead to a decrease of volume available for pressure generation, thus reducing the tongue driving force. The swallowing reflex is uncoordinated resulting in dyskinesia of the UES. Compensation may be achieved with a stronger oropharyngeal thrust and/or repeated swallows. Distal resections alter the pharyngoesophageal segment so that a functional obstruction results, combined with lower pressure amplitudes in the hypopharynx, reducing the pressure gradient necessary for bolus flow. This increasing resistance can be overcome by higher propulsive forces in the base of the tongue region. In case of additional lingual defects, deglutition is subject to decompensation, highlighting the major role of the tongue as a pressure generator for bolus passage.