Miliary Tuberculosis in Adults

Of 40 adults with miliary tuberculosis 24 had “overt” disease; in them miliary mottling was usually present on the chest radiograph, and tubercle bacilli were readily isolated from sputum, urine, or cerebrospinal fluid. In the remaining 16 patients the disease was termed “cryptic” because its usual clinical and radiographic features were absent. This cryptic type is as common as the overt type in patients over 60 years. In this series the peak age incidence was in the eighth decade, and possibly this increase in the incidence age is due to the breakdown of old tuberculous foci in patients with diminished immunological mechanisms.Cryptic miliary tuberculosis is a difficult diagnostic problem and should be suspected in any elderly patient, particularly a woman, who has an unexplained pyrexia, pancytopenia, or leukaemoid reaction. In 10 cases it was diagnosed by a therapeutic trial with para-aminosalicylic acid and isoniazid, a fall of temperature to normal (usually within a week), weight gain, a rise in haemoglobin, and increased well-being being the criteria of improvement The use of such a trial is strongly advocated as a specific method of diagnosing cryptic miliary tuberculosis.     

Taxi Cab Syndrome: A Review of the Extensive Genitourinary Pathology Experienced by Taxi Cab Drivers and What We Can Do to Help

This review consolidates knowledge regarding the extensive genitourinary pathology experienced by taxi cab drivers. Taxi cab, livery, truck, and other drivers all objectively and subjectively may have more voiding dysfunction, infertility, urolithiasis, bladder cancer, and urinary infections as compared with nonprofessional drivers; this is called taxi cab syndrome. Together with governmental and medical assistance, simple interventions—such as education, the addition of taxi relief stations, and possibly the use of sanitary urinary collection devices—to curb the progression of genitourinary disease in taxi drivers should be prospectively studied. It is postulated that many of these interventions may also benefit other groups of occupationally related infrequent voiders.Key words: Taxi cab syndrome, Infrequent voiders syndrome, Occupational hazard, Voiding dysfunction, Prostodynia, Infertility, UrolithiasisIn New York City, where taxi cabs flow like erythrocytes in a vast net of arteries, the drivers, New York’s backbone, often do not have sufficient flow themselves. This article demonstrates how the lack of adequate and accessible bathroom facilities in New York likely accounts for most of the genitourinary pathology that taxi drivers have. In fact, drivers represent only one of many occupations that contribute to voiding dysfunction as a result of inadequate bathroom access or other factors that lead to the inability to void regularly throughout the workday. These drivers represent the ultimate case study on how, using simple interventions, those who move us through New York City at an often bewildering speed may be helped.In the aptly worded article by Gany and colleagues,¹ “Every disease…man can get can start in this cab,” the cardiovascular risk factors of New York City taxi cabs are described in great detail. Gany and colleagues followed a cohort of South Asian immigrant taxi drivers, holding focus groups and administering surveys about the drivers’ perceptions of their own cardiovascular health. Musculoskeletal pain, diabetes, hypertension, vision problems, stress, obesity, and constipation were pervasive throughout the group. Additionally, urinary tract issues such as kidney problems, bladder dysfunction, and prostatism were noted. One of the participants attributed his onset of kidney problems to intentional infrequent urination, and said this was mostly “because you don’t have facilities at most places where you can stand and urinate.” Two other drivers with diabetes-induced polyuria also attributed their severe problem with this issue.¹     

The Spectrum of Extrapulmonary Tuberculosis

The incidence of new cases of extrapulmonary tuberculosis has remained constant, despite the decline in new cases of active pulmonary tuberculosis. This might be due to a delay in recognition, and particularly a lack of consideration of tuberculosis when the presenting symptoms are other than respiratory. Extrapulmonary tuberculosis should be considered in the differential diagnosis of bone, joint, genitourinary tract and central nervous system (CNS) diseases.To determine factors that might delay recognition and identification, 62 patients having extrapulmonary tuberculosis during 1969-1972 at the Los Angeles County-University of Southern California Medical Center were studied.Three quarters of these patients had had CNS, skeletal or genitourinary tuberculosis in equal distribution or 25 percent each. CNS involvement was seen frequently in the disseminated form. Presenting symptoms were protean and not specific, such as fever, anorexia, weight loss, cough, lymphadenopathy and neurologic abnormalities. Roentgenograms of the chest were abnormal in most. When a roentgenogram of the chest suggests pulmonary tuberculosis, signs and symptoms in other body systems should suggest extrapulmonary tuberculosis. If no abnormalities are seen on a roentgenogram of the chest, however, this does not preclude the diagnosis of extrapulmonary tuberculosis. Neither does a negative tuberculin skin test exclude the condition.Abnormal laboratory findings are common, especially in disseminated tuberculosis. These include various anemias, bone marrow disorders, hyponatremia due to inappropriate antidiuretic hormone syndrome. Analyses of pleural, peritoneal, pericardial and joint fluid usually show an exudate high in lymphocytes and occasionally low in glucose. Similar findings are seen in spinal fluid. The histological features of caseous or noncaseous granulomas are suggestive of but not specific for tuberculosis. Only culture of mycobacteria from sputum, urine, spinal fluid, pleural and other effusions and tissue biopsy specimens will yield a definitive diagnosis.Physicians must have a high index of suspicion to diagnose extrapulmonary tuberculosis, as it can resemble any disease in any organ system. Immediate therapy in the disseminated variety, sometimes even before a definite diagnosis can be made, may be lifesaving.     

END RESULTS IN PAROTID TUMORS

Management of parotid tumors can be based on a clinical classification of these lesions as being either “encapsulated” or infiltrating.The Warthin tumor (papillary cystadenolymphomatosum) is a benign encapsulated tumor, often occurring multicentrically or bilaterally especially in the lower pole area of the parotid. It is characterized clinically by its softness and fluctuation in size and a high incidence in elderly men.The so-called “capsule” of well demarcated mixed and mucoepidermoid tumors is represented by a condensation of host fibrous stroma, in the interstices of which tumor cells may be present.The “encapsulated” tumors should be excised with a “shell” of uninvolved parotid tissue. To do this safely, the facial nerve should first be isolated.Total parotidectomy is necessary only if the size of the tumor, the multiplicity of recurrences, or the infiltrating nature of the tumor are such that complete eradication of the primary site must be done.Radical neck dissection is never performed electively except in the small group of nonencapsulated infiltrating primary lesions.In a series of cases of previously untreated parotid tumors treated by the method outlined, the local parotid recurrence rate was less than 1 per cent.     

Clonal immune responses of Mycobacterium-specific γδ T cells in tuberculous and non-tuberculous tissues during M. tuberculosis infection

Background

We previously demonstrated that unvaccinated macaques infected with large-dose M.tuberculosis(Mtb) exhibited delays for pulmonary trafficking of Ag-specific αβ and γδ T effector cells, and developed severe lung tuberculosis(TB) and “secondary” Mtb infection in remote organs such as liver and kidney. Despite delays in lungs, local immunity in remote organs may accumulate since progressive immune activation after pulmonary Mtb infection may allow IFNγ-producing γδ T cells to adequately develop and traffic to lately-infected remote organs. As initial efforts to test this hypothesis, we comparatively examined TCR repertoire/clonality, tissue trafficking and effector function of Vγ2Vδ2 T cells in lung with severe TB and in liver/kidney without apparent TB.

Methodology/Principal Findings

We utilized conventional infection-immunity approaches in macaque TB model, and employed our decades-long expertise for TCR repertoire analyses. TCR repertoires in Vγ2Vδ2 T-cell subpopulation were broad during primary Mtb infection as most TCR clones found in lymphoid system, lung, kidney and liver were distinct. Polyclonally-expanded Vγ2Vδ2 T-cell clones from lymphoid tissues appeared to distribute and localize in lung TB granuloms at the endpoint after Mtb infection by aerosol. Interestingly, some TCR clones appeared to be more predominant than others in lymphocytes from liver or kidney without apparent TB lesions. TCR CDR3 spetratyping revealed such clonal dominance, and the clonal dominance of expanded Vγ2Vδ2 T cells in kidney/liver tissues was associated with undetectable or low-level TB burdens. Furthermore, Vγ2Vδ2 T cells from tissue compartments could mount effector function for producing anti-mycobacterium cytokine.

Conclusion

We were the first to demonstrate clonal immune responses of mycobacterium-specific Vγ2Vδ2 T cells in the lymphoid system, heavily-infected lungs and lately subtly-infected kidneys or livers during primary Mtb infection. While clonally-expanded Vγ2Vδ2 T cells accumulated in lately-infected kidneys/livers without apparent TB lesions, TB burdens or lesions appeared to impact TCR repertoires and tissue trafficking patterns of activated Vγ2Vδ2 T cells.     

THE USE OF BASIC DIETS IN THE TREATMENT OF NEPHRITIS

By the employment of what we are pleased to call a “basic diet,” the urinary acidity may be easily reduced to a pH of 7.00 or better.On such diets patients with chronic interstitial nephritis appear to improve, as evidenced by a decrease in blood pressure, albumin and casts in the urine and other symptoms of nephritis and arterial hypertension.     

Determination of phytic acid by gas chromatography–mass spectroscopy: application to biological samples

A GC–MS method is reported for the determination of phytic acid based on purification by anion-exchange chromatography, enzymatic hydrolysis of phytic acid to myo-inositol and derivation to trimethylsilyl derivative, with scyllo-inositol as an internal standard. Analytical features of the method are: limit of detection 9 μg l⁻¹ phytic acid, linear working range 18–500 μg l⁻¹ phytic acid, and coefficient of variation 1.9%. The method has been successfully applied to a variety of biological samples: various rat organs (kidney, liver, brain and bone), human plasma and urine and kidney stones. A comparative study of sample treatments, including deproteization, lipid extraction and the presence of a chelator, is also reported. Phytic acid amounts found in rat organs ranged from 1.07 g kg⁻¹ for bone to 32.0 g kg⁻¹ for brain. Phytic acid in human plasma was of the order of 0.14 mg l⁻¹. In kidney stones, phytic acid was found in calcium containing stones.     

Mealtime,Temporal, and Daily Variability of the Human Urinary and Plasma Metabolomes in a Tightly Controlled Environment

While metabolomics has tremendous potential for diagnostic biomarker and therapeutic target discovery, its utility may be diminished by the variability that occurs due to environmental exposures including diet and the influences of the human circadian rhythm. For successful translation of metabolomics findings into the clinical setting, it is necessary to exhaustively define the sources of metabolome variation. To address these issues and to measure the variability of urinary and plasma metabolomes throughout the day, we have undertaken a comprehensive inpatient study in which we have performed non-targeted metabolomics analysis of blood and urine in 26 volunteers (13 healthy subjects with no known disease and 13 healthy subjects with autosomal dominant polycystic kidney disease not taking medication). These individuals were evaluated in a clinical research facility on two separate occasions, over three days, while on a standardized, weight-based diet. Subjects provided pre- and post-prandial blood and urine samples at the same time of day, and all samples were analyzed by “fast lane” LC-MS-based global metabolomics. The largest source of variability in blood and urine metabolomes was attributable to technical issues such as sample preparation and analysis, and less variability was due to biological variables, meals, and time of day. Higher metabolome variability was observed after the morning as compared to the evening meal, yet day-to-day variability was minimal and urine metabolome variability was greater than that of blood. Thus we suggest that blood and urine are suitable biofluids for metabolomics studies, though nontargeted mass spectrometry alone may not offer sufficient precision to reveal subtle changes in the metabolome. Additional targeted analyses may be needed to support the data from nontargeted mass spectrometric analyses. In light of these findings, future metabolomics studies should consider these sources of variability to allow for appropriate metabolomics testing and reliable clinical translation of metabolomics data.     

THE SIGNIFICANCE OF “ALBUMINURIA” (PROTEINURIA)

“Albuminuria” is an inadequate term; proteins other than albumin commonly appear in the urine.Proteinuria seems to depend upon failure of the tubules to reabsorb protein which has filtered through glomeruli. Its occurrence may be the result of abnormal plasma proteins, glomeruli or tubules. Proteinuria need not always be the result of a renal lesion, but may actually cause one.When proteinuria is discovered, it should arouse curiosity about the patient in general, not merely about his kidneys. Other clinical information is needed in order that treatment be directed appropriately.     

MANDIBULAR HERPES ZOSTER—With Report on the Use of Cortisone in a Case with Geniculate Ganglion Symptoms

Herpes zoster, an acute specific viral infection, occurs more commonly than is generally supposed. It should be differentiated from other diseases involving the ear and skin; it must be considered as a possible etiologic agent in some palsies of the facial, glossopharyngeal or vagal nerves.The type of cephalic herpes zoster should be carefully differentiated; cases involving the “geniculate zone” may be other than “Ramsay Hunt''s syndrome.” This syndrome is now defined as a herpes zoster eruption of the external ear at the “geniculate zone” with involvement of the seventh or seventh and eighth nerves.The “topognostic” method is the best for determining the level at which the facial nerve has been affected.It is questioned whether there is a single outstanding therapeutic agent for this disease. Cortisone had no apparent therapeutic effect in a case reported herein.     

Chest Radiographic Patterns and the Transmission of Tuberculosis: Implications for Automated Systems

BackgroundComputer-aided detection to identify and diagnose pulmonary tuberculosis is being explored. While both cavitation on chest radiograph and smear-positivity on microscopy are independent risk factors for the infectiousness of pulmonary tuberculosis it is unknown which radiographic pattern, were it detectable, would provide the greatest public health benefit; i.e. reduced transmission. Herein we provide that evidence.Objectives1) to determine whether pulmonary tuberculosis in a high income, low incidence country is more likely to present with “typical” adult-type pulmonary tuberculosis radiographic features and 2) to determine whether those with “typical” radiographic features are more likely than those without such features to transmit the organism and/or cause secondary cases.MethodsOver a three-year period beginning January 1, 2006 consecutive adults with smear-positive pulmonary tuberculosis in the Province of Alberta, Canada, were identified and their pre-treatment radiographs scored by three independent readers as “typical” (having an upper lung zone predominant infiltrate, with or without cavitation but no discernable adenopathy) or “atypical” (all others). Each patient’s pre-treatment bacillary burden was carefully documented and, during a 30-month transmission window, each patient’s transmission events were recorded. Mycobacteriology, radiology and transmission were compared in those with “typical” versus “atypical” radiographs.FindingsA total of 97 smear-positive pulmonary tuberculosis cases were identified, 69 (71.1%) with and 28 (28.9%) without “typical” chest radiographs. “Typical” cases were more likely to have high bacillary burdens and cavitation (Odds Ratios and 95% Confidence Intervals: 2.75 [1.04–7.31] and 9.10 [2.51–32.94], respectively). Typical cases were also responsible for most transmission events—78% of tuberculin skin test conversions (p<0.002) and 95% of secondary cases in reported close contacts (p<0.01); 94% of secondary cases in “unreported” contacts (p<0.02).ConclusionAs a group, smear-positive pulmonary tuberculosis patients with typical radiographic features constitute the greatest public health risk. This may have implications for automated detection systems.     

尿源干细胞在泌尿生殖系统再生领域的研究进展

近年来,随着尿源干细胞成功从尿液中提取,人们一直在探究其在人体各系统再生领域中的应用,尤其在泌尿生殖系统再生领域的研究较多。目前文献报道可见,尿源干细胞在肾脏、输尿管、膀胱、尿道和男性生殖器官等泌尿生殖系统的再生领域展现出一定的组织重建及修复能力,其应用前景广阔,本文就尿源干细胞在泌尿生殖系统再生领域的研究进展作一述评。     

Rheostats and Toggle Switches for Modulating Protein Function

The millions of protein sequences generated by genomics are expected to transform protein engineering and personalized medicine. To achieve these goals, tools for predicting outcomes of amino acid changes must be improved. Currently, advances are hampered by insufficient experimental data about nonconserved amino acid positions. Since the property “nonconserved” is identified using a sequence alignment, we designed experiments to recapitulate that context: Mutagenesis and functional characterization was carried out in 15 LacI/GalR homologs (rows) at 12 nonconserved positions (columns). Multiple substitutions were made at each position, to reveal how various amino acids of a nonconserved column were tolerated in each protein row. Results showed that amino acid preferences of nonconserved positions were highly context-dependent, had few correlations with physico-chemical similarities, and were not predictable from their occurrence in natural LacI/GalR sequences. Further, unlike the “toggle switch” behaviors of conserved positions, substitutions at nonconserved positions could be rank-ordered to show a “rheostatic”, progressive effect on function that spanned several orders of magnitude. Comparisons to various sequence analyses suggested that conserved and strongly co-evolving positions act as functional toggles, whereas other important, nonconserved positions serve as rheostats for modifying protein function. Both the presence of rheostat positions and the sequence analysis strategy appear to be generalizable to other protein families and should be considered when engineering protein modifications or predicting the impact of protein polymorphisms.     

Primary amoebic meningoencephalitis in Britain

Primary amoebic meningoencephalitis is caused by amoebae of the genera Naegleria and Hartmannella (Acanthamoeba), which ordinarily are free-living saprophytes. The infection may be acquired from fresh water—for example, while bathing—the amoebae invading the nasal mucosa and reaching the meninges and brain along the olfactory nerve filaments. The disease is designated “primary” to distinguish it from meningocerebral infection caused by the parasitic amoebae, particularly Entamoeba histolytica, which invade the central nervous system only as a result of dissemination in the blood stream from lesions in other parts of the body.During histological reappraisal of old specimens in a medical museum in London an instance of amoebic meningoencephalitis histologically indistinguishable from the published cases has been found. The specimen dates from 1909. The patient was said to be from Essex. What may have been another case, seen in Northern Ireland in 1937, is also described briefly. These observations may indicate that this disease occurs in the British Isles.Primary amoebic meningoencephalitis should be considered in the differential diagnosis of every case of acute meningitis.     

Branching Morphogenesis: From Cells to Organs and Back

Many animal organs, such as the lung, the kidney, the mammary gland, and the vasculature, consist of branched tubular structures that arise through a process known as “branching morphogenesis” that results from the remodeling of epithelial or endothelial sheaths into multicellular tubular networks. In recent years, the combination of molecular biology, forward and reverse genetic approaches, and their complementation by live imaging has started to unravel rules and mechanisms controlling branching processes in animals. Common patterns of branch formation spanning diverse model systems are beginning to emerge that might reflect unifying principles of tubular organ formation.     

Hydronephrotic Urine in the Obstructed Kidney Promotes Urothelial Carcinoma Cell Proliferation,Migration, Invasion through the Activation of mTORC2-AKT and ERK Signaling Pathways

Obstructive nephropathy is the most common presentation of urothelial carcinoma. The role of the urine in the obstructed kidney namely “hydronephrotic urine” in urothelial carcinoma has not been extensively explored. This study aims to evaluate whether hydronephrotic urine in the obstructed kidney could promote urothelial carcinoma. The hydronephrotic urine was collected from the obstructed kidneys of Sprague-Dawley rats induced by different periods of unilateral ureteral obstruction (UUO). By the inhibition of LY294002 and PD184352, we confirm that hydronephrotic urine promotes urothelial carcinoma cell (T24) and immortalized normal urothelial cells (E6) proliferation, migration and invasion in a dose-dependent manner through the activation of the mTORC2-AKT and ERK signaling pathways. Hydronephrotic urine also increases the expression of cyclin-D2, cyclin-B and CDK2. It also decreases the expression of p27 and p21 in both urothelial carcinoma cells and normal urothelial cells. By the protein array study, we demonstrate that many growth factors which promote tumor cell survival and metastasis are over-expressed in a time-dependent manner in the hydronephrotic urine, including beta-FGF, IFN-γ, PDGF-BB, PIGF, TGF-β, VEGF-A, VEGF-D and EGF. These results suggest that hydronephrotic urine promotes normal and malignant urothelial cells proliferation, migration and invasion, through the activation of the mTORC2-AKT and ERK signaling pathways. Further investigation using live animal models of tumor growth may be needed to clarify aspects of these statements.     

INITIAL CARE OF ACUTE BACK INJURIES

The mechanism of injury to the back should be obtained with the utmost accuracy and set down in the history as a separate paragraph under that heading. This is usually best obtained by questioning and requestioning the patient during the course of the examination. A history of any previous back affections should also be obtained at the first visit.The detailed examination of the back is not complete without a general physical examination.X-ray studies should be done immediately in all cases in which the injury has been caused by direct violence or forceful indirect violence (as in “jackknife” injury).Terms such as “disc disease,” “ruptured intervertebral disc” and various others that convey a similar meaning should not be used as the initial diagnosis and should be withheld until such a diagnosis is definitely established.The plan of treatment may include a period in hospital or of rest at home, or it may be carried out with the patient ambulatory. Corsets and braces should be prescribed only when they are to serve a definite function and the same can be said of physiotherapy.     

Response to Vitamin B12 and Folic Acid in Myalgic Encephalomyelitis and Fibromyalgia

Background

Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections, in vital combination with oral folic acid. However, there is no established algorithm for individualized optimal dosages, and rate of improvement may differ considerably between responders.

Objective

To evaluate clinical data from patients with ME, with or without fibromyalgia, who had been on B12 injections at least once a week for six months and up to several years.

Methods

38 patients were included in a cross-sectional survey. Based on a validated observer’s rating scale, they were divided into Good (n = 15) and Mild (n = 23) responders, and the two groups were compared from various clinical aspects.

Results

Good responders had used significantly more frequent injections (p<0.03) and higher doses of B12 (p<0.03) for a longer time (p<0.0005), higher daily amounts of oral folic acid (p<0.003) in good relation with the individual MTHFR genotype, more often thyroid hormones (p<0.02), and no strong analgesics at all, while 70% of Mild responders (p<0.0005) used analgesics such as opioids, duloxetine or pregabalin on a daily basis. In addition to ME, the higher number of patients with fibromyalgia among Mild responders was bordering on significance (p<0.09). Good responders rated themselves as “very much” or “much” improved, while Mild responders rated “much” or “minimally” improved.

Conclusions

Dose-response relationship and long-lasting effects of B12/folic acid support a true positive response in the studied group of patients with ME/fibromyalgia. It’s important to be alert on co-existing thyroid dysfunction, and we suspect a risk of counteracting interference between B12/folic acid and certain opioid analgesics and other drugs that have to be demethylated as part of their metabolism. These issues should be considered when controlled trials for ME and fibromyalgia are to be designed.     

Tuberculosis: A Challenge to the General Practitioner

Of 157 patients dying of tuberculosis in Ontario (1960) 132 (87.4%) suffered from the pulmonary form of the disease (incidence 2.6 per 100,000). In the same year, 1632 of 1847, or 88.3%, active new cases reported had the pulmonary type and 183 additional cases were reported without details as to type of disease. Thus, in 1960, a total of 2030 new cases of tuberculosis were reported in Ontario.Of 1367 patients with pulmonary tuberculosis (reinfection type), 357 (26.1%) had “far advanced” disease and 613 (44.8%) had “moderately advanced” disease.This high percentage of patients with “moderately advanced” to “far advanced” disease at the time of diagnosis constitutes the real challenge to physicians in private practice, who made the diagnosis in 45% of cases.Emergence of resistant strains of bacteria increases the urgency of prompt diagnosis and treatment. The most vulnerable population segment is the 15-30 year age-group, many of whom are negative intracutaneous reactors. A high index of suspicion is necessary, particularly in certain segments of the population with a high incidence of infection, combined with a careful history, meticulous physical examination, intracutaneous tests, chest and other radiographs, and appropriate bacteriological studies.     

Partly transparent young legume pods: Do they mimic caterpillars for defense and simultaneously enable better photosynthesis?

Being partly or fully transparent as a defense from predation is mostly known in various groups of aquatic animals and various terrestrial arthropods. Plants, being photosynthetic and having cell walls made of various polymers, cannot be wholly transparent. In spite of these inherent limitations, some succulent plant species of arid zones have partially transparent “windows” in order to perform photosynthesis in their below-ground leaves, as defense from herbivores as well as for protection from harsh environmental conditions. Similarly, transparent “windows” or even wholly transparent leaves are found in certain thick or thin, above-ground organs irrespective of aridity. The young pods of various wild annual Mediterranean legume species belonging to the genera Lathyrus, Pisum and Vicia are partly transparent and may therefore look like caterpillars when viewed with back illumination. I propose that this character serves 2 functions: (1) being a type of defensive caterpillar mimicry that may reduce their consumption by various herbivores in that very sensitive stage, and (2) simultaneously allowing better photosynthesis in the rapidly growing seeds and pods. Unlike animals that are transparent for either defensive or aggressive crypsis, in the case of young legume pods it allows them to visually mimic caterpillars for defense.