The influence of HIV status on the duration of chemoradiotherapy for anal squamous cell carcinoma.

BACKGROUND: The HIV epidemic has changed the demographic of patients with anal squamous cell carcinoma. The influence of HIV status on the ability to complete standard chemoradiotherapy was studied. METHODS: A retrospective analytic observational study was conducted of all patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital radiation oncology department with anal squamous cell carcinoma from January 2014 to December 2016. Standard chemoradiotherapy was offered to all patients. Stage of anal squamous cell carcinoma, HIV status and cluster of differentiation 4 (CD4) levels were measured and compared in groups. We considered a maximum of 42 days as complete therapy without delay. RESULTS: Ninety-two patients with anal squamous cell carcinoma were identified, of whom 67 were seen with the intention to treat and had known HIV status, of whom 59 received chemoradiotherapy. Eighty-eight per cent were people living with HIV (PLWH). PLWH were younger (p < 0.001) and less likely to receive full-dose chemotherapy (63%, p = 0.41). No patients presented in stage 1. More than 60% presented in stage 3. Fifty-six per cent of PLWH and 57% of HIV-negative patients were able to complete the 50 Gy radiation in 42 days (p = 1.0). CD4 above 200 did not impact therapy (p = 0.71). CONCLUSION: HIV status of anal squamous cell carcinoma has minimal impact on the duration of chemoradiotherapy.

It's contrary - comorbidity does not affect survival of South Africans with colorectal cancer: An analysis from the Colorectal Cancer in South Africa cohort.

BACKGROUND: The Colorectal Cancer South Africa (CRCSA) study is an observational cohort of patients with colorectal cancer (CRC) in Johannesburg, South Africa (SA). We found that the mean age at the time of CRC diagnosis was 56.6 years, consistent with studies from SA and sub-Saharan Africa. In high-income settings, comorbidity adversely affects CRC survival, and patients are substantially older at the time of CRC diagnosis. Given the younger age at CRC diagnosis in the CRCSA cohort, we hypothesised that comorbidity may be less prevalent and have little impact on CRC survival. OBJECTIVES: To determine the prevalence of comorbidity and whether comorbidity adversely affects overall survival (OS) of CRC patients. METHODS: Patients enrolled in the CRCSA study between January 2016 and July 2018 were included. The cohort comprised a convenience sample of adults with histologically confirmed CRC, treated at the University of the Witwatersrand Academic Teaching Hospital Complex. Demographic, clinical and histological variables were collected at baseline and participants were followed up for OS. The Charlson comorbidity index (CCI) scoring system was used to classify participants as 'no comorbidity' (CCI score 0) and '1 or more comorbidities' (CCI score ≥1). A descriptive analysis of the cohort was undertaken, while survival across comorbidity groups was compared by the Kaplan-Meier method and Cox proportional hazards (PH) regression models. Multivariable Cox PH regression was performed to examine the effect of comorbidity on survival (unadjusted) and then adjusted for variables. RESULTS: There were 424 participants, and the mean (standard deviation) age was 56.6 (14.1) years (range 18 - 91). Only 19.1% of participants had ≥1 comorbidities, of which diabetes mellitus was most frequent (12.3%), followed by chronic obstructive pulmonary disease (4.7%) and cardiovascular disease (3.1%). There was no significant difference in unadjusted and adjusted risk of death for the group with ≥1 comorbidities compared with those with no comorbidity. However, an incidental finding showed a significantly increased risk of death for those receiving potentially curative treatment later than 40 days after CRC diagnosis. CONCLUSIONS: In the CRCSA cohort from Johannesburg, comorbidity is uncommon, with no significant adverse effect on OS. If potentially curative treatment is initiated within 40 days of CRC diagnosis, OS could be improved. To fully understand the epidemiology of CRC in SA, population-based registries are essential, and future research should aim to identify health system failures that lead to delays in intervention beyond 40 days in patients with CRC.

The 'ins and outs' of colonoscopy at Wits Donald Gordon Medical Centre, South Africa: A practice audit of the outpatient endoscopy unit.

BACKGROUND: In South Africa, there are no national guidelines for the conduct or quality assessment of colonoscopy, the gold standard for investigation and diagnosis of bowel pathology. OBJECTIVES: To describe the clinical profile of patients and evaluate the practice of colonoscopy using procedural quality indicators at the Wits Donald Gordon Medical Centre (WDGMC) outpatient endoscopy unit (OEU). METHODS: We conducted a prospective, clinical practice audit of colonoscopies performed on adults (≥18 years of age). A total of 1 643 patients were included in the study and variables that were collected enabled the assessment of adequacy of bowel preparation, length of withdrawal time and calculation of caecal intubation rate (CIR), polyp detection rate (PDR) and adenoma detection rate (ADR). We stratified PDR and ADR by sex, age, population group, withdrawal time and bowel preparation. CIR, PDR and ADR estimates were compared between patient groups by the χ2 test; Fisher's exact test was used for 2 × 2 tables. A p-value <0.05 was used. Benchmark recommendations by the American Society for Gastrointestinal Endoscopy (ASGE)/American College of Gastroenterology (ACG) Task Force on Colorectal Cancer (CRC) were used in this audit to assess individual endoscopist performance and that of the endoscopy unit as a whole. RESULTS: The mean age of patients was 55.7 (standard deviation (SD) 14.4; range 18 - 91) years, ~60% were female, and the majority (75.5%) were white. Of the outpatients, 77.6% had adequate bowel preparation (ASGE/ACG benchmark ≥85%). The CIR was 97.0% overall, and screening colonoscopy was 96.3% (ASGE/ACG benchmark ≥90% overall and ≥95% for screening colonoscopies). The median withdrawal time for negative-result screening colonoscopies was 5.7 minutes (interquartile range (IQR) 4.2 - 9.3; range 1.1 - 20.6) (ASGE/ACG benchmark ≥ 6minutes), and PDR and ADR were 27.6% and 15.6%, respectively (ASGE/ACG benchmark ADR ≥25%). We demonstrated a 23.7% increase in PDR and 14.1% increase in ADR between scopes that had mean withdrawal times of ≥6 minutes and <6 minutes, respectively. Although the number of black Africans in the study was relatively small, our results showed that they have similar ADRs and PDRs to the white population group, contradicting popular belief. CONCLUSIONS: The WDGMC OEU performed reasonably well against the international guidelines, despite some inadequacy in bowel preparation and lower than recommended median withdrawal times on negative-result colonoscopy. Annual auditing of clinical practice and availability of these data in the public domain will become standard of care, making this audit a baseline for longitudinal observation, assessing the impact of interventions, and contributing to the development of local guidelines.

The prevalence and influence of significant psychiatric abnormalities in men undergoing comprehensive management of organic erectile dysfunction.

Psychiatric factors are etiologically important in a proportion of patients with erectile dysfunction. We determined the prevalence of psychopathology and the impact it has on current erectile dysfunction (ED) assessment and management. A group of 120 consecutive men with ED presenting to the Human Sexuality Clinic for the first time was prospectively investigated. All patients participated in a standardized evaluative protocol, including history, physical exam, assessment by a psychiatrist (using DSM-IV criteria), selective hormonal screen, and diagnostic intracavernosal injection. Follow-up appointments were to discuss diagnostic findings and, eventually, treatment choices. The prevalence of significant psychiatric pathology, excluding interview stress, was 33%. Only 16 of 40 cases were recognized and highlighted in the initial assessments by urological staff. There was no significant difference in the modalities of treatment choices between patients with psychiatric problems and those without. 10% of the patients had multiple organic risk factors, normal ICI, and significant psychiatric pathology. Psychopathology or emotional factors play a significant role in the etiology of ED and they are difficult to identify in a non-directed assessment. Even in the face of significant vascular risk factors, psychological abnormalities may be the primary etiology. Treating the 'phallodynamically challenged' individual without adequately addressing the possible presence of psychopathology, will account for treatment failures and have the potential for leaving untreated serious emotional problems.

Topical nitroglycerin: a potential treatment for impotence.

The effect of 2 per cent nitroglycerin paste applied to the penile shaft of impotent subjects was evaluated in a placebo controlled double-blind study under laboratory conditions. After application of nitroglycerin paste or a placebo ointment base, penile tumescence was recorded through a strain gauge transducer while subjects viewed an erotic video presentation. Relative to the placebo paste the number of subjects demonstrating an increase in penile circumference after nitroglycerin (18 of 26) was significantly different than all other outcome possibilities (p less than 0.05). Noninvasive vascular assessment by ultrasonography demonstrated an increase in diameter and blood flow in the cavernous arteries after application of nitroglycerin paste. Nitroglycerin paste increases blood flow in the cavernous arteries and improves tumescence after erotic stimulation. This agent may represent a new therapy for impotence.

Oral and transcutaneous pharmacologic agents in the treatment of impotence.

The pharmacologic treatment of erectile failure is now a reality. However, current agents have major drawbacks. Some require invasive administration, whereas others offer only marginal effect. The use of hormones should be limited to well-documented cases of endocrine dysfunction. Oral and transcutaneous agents remain experimental, but new drugs are under investigation and show early encouraging results.

Double-blind trial of yohimbine in treatment of psychogenic impotence.

48 subjects meeting strict diagnostic criteria for psychogenic impotence took part in a 10 week placebo-controlled, double-blind, partial crossover trial of yohimbine (18 mg a day) for restoring erectile function. At the end of the first arm of the trial 62% of the yohimbine group and 16% of the placebo group reported some improvement in sexual function (chi 2 = 10.41, df = 2, p less than 0.05). 21% of the originally placebo-treated group noticed some improvement over pre-treatment levels when they were put on yohimbine in the second arm of the trial. Overall 46% of those who received yohimbine reported a positive response to the drug, a response rate very similar to that observed in a previous study of patients with organic impotence. Response to yohimbine thus seems to be unrelated to current groupings of the cause of impotence. Yohimbine is a safe treatment for psychogenic impotence that seems to be as effective as sex and marital therapy for restoring satisfactory sexual functioning.

Is yohimbine effective in the treatment of organic impotence? Results of a controlled trial.

Yohimbine is an alpha-adrenoceptor blocker that has been used in the treatment of erectile dysfunction. Adequate trials of this substance in a clearly defined organically impotent population are not available. We conducted a randomized, controlled study with partial cross-over of yohimbine versus placebo in 100 organically impotent men. The first phase of the study showed a positive response in 42.6 per cent of the patients receiving yohimbine versus 27.6 per cent in the placebo group. Although favorable to the test medication these values did not reach statistical significance (p equals 0.42). A similar pattern was noted in the second phase of the study. The over-all response rate of 43.5 per cent was consistent with a previous noncontrolled trial but it was much lower than previous studies. The response rate of organically impotent patients to yohimbine is at best marginal. Owing to its ease of administration, safety and modest effect it still is used in those patients who do not accept more invasive methods. Adrenoceptors are involved in the erectile process, although other neurotransmitter systems also are putative modulators of penile erection, including cholinergic, dopaminergic and vasoactive intestinal polypeptide pathways. It is beyond reasonable expectation that a single agent be of value for all cases of organic impotence. However, yohimbine has shown modest effectiveness at the doses used in this trial (18 mg. per day). Higher doses or a different route of administration may produce different effects.

Screening assessment of penile tumescence and rigidity. Clinical test of Snap-Gauge.

A study was conducted to investigate the clinical usefulness of the Snap-Gauge, a device intended to provide an economical alternative to complete nocturnal penile tumescence (NPT) recording. Twenty-one patients were assessed using the Snap-Gauge either during NPT recording or during the corporeal calibration test (CCT), or both. Patient acceptance of the device was excellent. The results indicate a fair degree of consistency between the Snap-Gauge and CCT measurements. The Snap-Gauge and NPT findings were less consistent. The results suggest that the Snap-Gauge is a reliable and useful screening device for assessing impotent patients. However, it is not an adequate substitute for a more complete NPT monitoring with polysomnographic recording.

The pharmacokinetics of yohimbine in man.

The kinetic disposition of yohimbine was examined in eight young male subjects following a single oral dose of 10 mg yohimbine hydrochloride. The drug was rapidly absorbed (absorption half-time 0.17 +/- 0.11 h) and rapidly eliminated from the plasma (elimination half-life 0.60 +/- 0.26 h). This clearance of yohimbine from plasma was constant over approximately 10 elimination half-lives, suggesting that distribution into a second pharmacokinetically distinct compartment was not responsible for the rapid decline in plasma yohimbine levels. Urinary excretion and the partitioning of the drug into red blood cells (RBC) was investigated. In the 24 h following oral administration of the drug, virtually no yohimbine was eliminated in the urine (0.35 +/- 0.50% of the administered dose). Furthermore, only 20% of blood-borne yohimbine was located in RBC. These results suggest that yohimbine is eliminated primarily through metabolism since the rapid plasma clearance of yohimbine was not the result of renal elimination or sequestration by RBC.

Prevalence and significance of tobacco smoking in impotence.

We investigated the incidence of cigarette smoking in a sample of patients and compared these figures with estimates of smoking among males in the general population. Among 178 impotent patients the number of current smokers (58.4%) and current ex-smokers combined (81%) was significantly higher than would be expected among males in the general population. In each age group, and at all levels of tobacco use, impotent patients smoked more than would be expected from population estimates. Smoking and nonsmoking impotent patients did not differ in terms of their hormonal profile; however, mean penile blood pressure (PBI) was lower among patients who smoked than among those who did not. A significantly higher proportion (20.9%) of impotent patients with a history of smoking showed abnormally low PBI compared with nonsmoking patients (8.8%). This study adds to preliminary evidence that smoking may be a significant risk factor in impotence, and its effects are evident in the small vasculature.

The unreliability of nocturnal penile tumescence recording as an outcome measurement in the treatment of organic impotence.

We investigated the degree of congruence between outcome measures used to evaluate pharmacological treatment of impotence. After a comprehensive multidisciplinary assessment 17 patients were treated with an adrenergic blocker during an 8-week interval. Nocturnal penile tumescence recordings were made before treatment (as part of the assessment procedure) and at its conclusion. As part of a larger study the use of nocturnal penile tumescence monitoring has been examined as a possible outcome measure. Patient and partner self-reports also were used to evaluate treatment outcome. A comparison of patient and partner self-reports with nocturnal penile tumescence records showed little agreement between the 2 measures. These findings suggest that despite its intuitive appeal as an index of erectile function nocturnal penile tumescence recording is not a reliable index of therapeutic effectiveness. Furthermore, these findings lend support to the hypothesis that nocturnal penile tumescence and sexual erections may be separate phenomena, perhaps under the control of different mechanisms.

Sub-nanogram analysis of yohimbine and related compounds by high-performance liquid chromatography.

A sensitive (50 pg/ml) method is described for the analysis of yohimbine in blood by high-performance liquid chromatography with fluorescence detection. The chromatographic behaviour of eserine (employed as internal standard), reserpine, corynanthine, yohimbinic acid, and yohimbine are examined on a series of reversed-phase and normal-phase chromatographic columns with methanol-water mobile phases.

Neuropsychological function in diabetic patients with neuropathy.

Psychometric examination of a group of diabetic patients and a group of age-matched controls failed to provide evidence of impaired intellectual functioning in the diabetic group. The cognitive status of the diabetics was not related to the duration of the illness, the age at diagnosis, or clinical ratings of peripheral or autonomic neuropathy.

Psychiatric aspects of diabetes mellitus.

A descriptive study of the psychiatric findings in 50 insulin--dependent diabetics is presented. Among the symptoms found were a marked reduction in energy level, increased fatigue and irritability, depression, and delayed psychosexual maturation. Diabetes mellitus is commonly considered to be a disease that, if properly controlled, allows the patient to lead a relatively normal life. We found, however, that these symptoms often made the patients' lives uncomfortable, reduced their functional capacity, disrupted their family life, and disturbed the adolescence of those who were affected at an early age.

Endocrine dysfunction in impotence: incidence, significance and cost-effective screening.

A comprehensive evaluation of impotence includes assessment of the functional integrity of the hypothalamic-pituitary-gonadal axis. However, little is known about the incidence or significance of hormonal abnormalities in an unselected group of men with erectile failure. A systematic multidisciplinary, multidimensional assessment of 256 impotent men showed clearly an organic etiology in 35.9 per cent, psychogenic in 38.3 per cent and mixed or uncertain in 25.8 per cent. The incidence of hypothalamic-pituitary-gonadal axis abnormalities in the entire group was 17.5 per cent but in only 12.1 per cent did they contribute clearly to erectile dysfunction. A cost-effective screening of the endocrine system in impotent men includes a thorough history and physical examination, and a serum testosterone determination. More sophisticated and expensive investigations should be reserved for patients with a history of drug use known to induce hormonal abnormalities or with somatic evidence of hypogonadism and a depressed serum testosterone level.

Functional correlates of reduced central conduction velocity in diabetic subjects.

In a previous publication, we presented evidence of slowed conduction speed in the central nervous systems of insulin-dependent diabetic subjects, manifest in a delay in the latency of the brainstem auditory-evoked response (BAER). In this article, we present the results of a multivariate study conducted on a larger sample of 50 insulin-dependent, adult diabetic subjects. The purpose of the study was to determine some of the functional correlates of the BAER delay; each patient received an assessment of the BAER, the late auditory-evoked potential (EP), the conduction velocities of the sural, median, and common peroneal nerves, and intellectual and emotional function, in addition to neurologic and audiologic examinations. A nondiabetic control group was matched with the diabetic group as to age and sex. The results indicated a delay in the latency of wave V, and in interpeak latencies I-III and I-V, of the BAER. The most reliable effect was on interpeak latency I-V; this suggested that the locus of the delay was in the central auditory projections, rather than in the acoustic nerve. In addition, BAER waves I, II, III, IV, and V were reduced in amplitude, as was the N1 component of the late auditory EP; the most reliable reduction in amplitude was in wave V. The effect was similar in magnitude for males and females, relative to their counterparts in the control group. The slowed BAER response appeared early in the disease and was not related to the duration of insulin treatment. It was correlated with a chronic loss of energy and the presence of sexual dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the urological assessment in impotence: findings with a new diagnostic rating scale.

We report the findings of a critical evaluation of urological assessment in impotence. Initially, a rating scale (Q scale) was developed, which included the individual elements of the urological assessment, such as testicular size, serum testosterone level and so forth. The items in the scale were derived from the files of patients with erectile dysfunction and were scaled according to predetermined categories. Following this, the rating scale was applied to 67 impotent patients in whom the etiology had been established clearly using criteria that were independent of the urological assessment (that is a psychiatric interview and nocturnal penile tumescence evaluation). Statistical analysis of the results indicated that the 2 diagnostic groups differed significantly on a number of the individual scale items. However, no single item by itself could be used as a reliable indicator of etiology. Further analysis indicated that when the items were considered in combination, rather than singly, etiology was identified correctly in 95 per cent of the patients in the sample. Replication of these findings in a cross-validation study will help to standardize the urological assessment and to promote the development of a common language to facilitate communication in this field.

Penile elongation: a method for the screening of impotence.

Circumferentially assessed penile responses less than 10 per cent of maximal tumescence usually are regarded as random variation. However, several investigators have hypothesized that one of the initial responses to sexual stimulation is a lengthening of the penile shaft. Circumferential measurements detect this lengthening as a decrease in penile circumference. Two experiments were conducted to investigate this hypothesis. During the first experiment penile circumference changes were monitored at 2 levels of voltage sensitivity. A reliable voltage decrease was observed for all subjects immediately after the introduction of an erotic stimulus. In the second experiment the penis was videotaped to determine the magnitude of penile lengthening that occurred during the circumferential decrease. The results indicated that a substantial penile length change occurred (mean 34.5 per cent of the total erection length change) before any diameter increase was evident. A small number of impotent patients with a clear etiology were investigated using this new test. The results suggest that penile elongation occurs in the absence of full erections in patients with psychogenic impotence, while circumferential and longitudinal changes do not appear after visual erotic stimuli in organically impotent patients. The penile elongation test may prove useful in the etiological screening of impotent patients.

A new device for diagnostic screening of nocturnal penile tumescence.

An erectometer for the measurement of sleep erections is described. Comparative studies using simultaneously strain gauges and the new device indicate that it possesses a significant potential for valid measurement of the circumferential increase that may occur during sleep. Because of its reliability, simplicity and low cost the erectometer is proposed as a screening procedure or as a diagnostic alternative when sleep laboratory facilities are not feasible.